Toxin-based therapeutic approaches

Toxins

Volumn 2, Issue 11, 2010, Pages 2519-2583

  Shapira, Assaf ^a   Benhar, Itai ^a  

^a TEL AVIV UNIVERSITY   (Israel)

Author keywords

Anthrax; Diphtheria toxin; Immunotoxins; Pseudomonas exotoxin a; Ricin; Suicide gene; Targeting; Toxins

Indexed keywords

BACTERIAL TOXIN; BL 22; CD19 ANTIGEN; CD22 ANTIGEN; CD30 LIGAND; CRM 107; DAB 389; DENILEUKIN DIFTITOX; DIPTHERIA TOXIN; DT 388; EXOTOXIN A; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMMUNOTOXIN; IMMUNOTOXIN CD19; IMMUNOTOXIN CD22; IMMUNOTOXIN CD25; IMMUNOTOXIN CD30; IMMUNOTOXIN LMB1; IMMUNOTOXIN LMB2; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR ALPHA; MATRIX METALLOPROTEINASE; RIBOSOME INACTIVATING PROTEIN; TOXIN; TRANSFERRIN RECEPTOR; UNCLASSIFIED DRUG; UROKINASE RECEPTOR;

ASTHENIA; B CELL LYMPHOMA; BLADDER CANCER; BRAIN EDEMA; CELL DEATH; COLORECTAL CARCINOMA; CONTINUOUS INFUSION; CYTOTOXICITY TEST; DRUG APPROVAL; DRUG EFFICACY; DRUG INDICATION; DRUG TARGETING; DYSPNEA; EDEMA; ENZYME ACTIVITY; FATIGUE; GENE OVEREXPRESSION; GLIOBLASTOMA; GLIOMA; HEMOLYTIC UREMIC SYNDROME; HODGKIN DISEASE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOALBUMINEMIA; HYPOPHYSIS TUMOR; LIVER CELL CARCINOMA; MELANOMA; MYALGIA; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; PROTEIN TARGETING; REVIEW; RHABDOMYOSARCOMA; SIDE EFFECT; SUICIDE GENE THERAPY; T CELL LYMPHOMA; TACHYCARDIA; TARGET CELL DESTRUCTION; TOXIN ANALYSIS; TOXIN STRUCTURE; TREATMENT RESPONSE; VASCULAR DISEASE; VASCULAR LEAK SYNDROME; VIRAL GENE DELIVERY SYSTEM; VIRUS INFECTION; WEAKNESS;

ANIMALS; ANTINEOPLASTIC AGENTS; BACTERIAL TOXINS; BIOLOGICAL EVOLUTION; CELL DEATH; DRUG EVALUATION, PRECLINICAL; FEMALE; GENES, TRANSGENIC, SUICIDE; GENETIC THERAPY; HUMANS; IMMUNOTOXINS; MALE; PHARMACEUTICAL PREPARATIONS; PLANT EXTRACTS; PLANTS, TOXIC; TOXINS, BIOLOGICAL;

PSEUDOMONAS EXOTOXIN;

EID: 79952265972     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins2112519     Document Type: Review

References (535)

1. Kostrzewa, R.; Segura-Aguilar, J. Botulinum neurotoxin: Evolution from poison, to research tool-onto medicinal therapeutic and future pharmaceutical panacea. Neurotox. Res. 2007, 12, 275-290.
2. Mahajan, S.T.; Brubaker, L. Botulinum toxin: From life-threatening disease to novel medical therapy. Am. J. Obstet. Gynecol. 2007, 196, 7-15.
3. Erbguth, F.J. From poison to remedy: The chequered history of botulinum toxin. J. Neur. Transm. 2008, 115, 559-565.
4. Truong, D.D.; Stenner, A.; Reichel, G. Current Clinical Applications of Botulinum Toxin. Curr. Pharm. Design 2009, 15, 3671-3680.
5. Winau, F.; Westphal, O.; Winau, R. Paul Ehrlich-In search of the magic bullet. Microb. Infect. 2004, 6, 786-789.
6. Bosch, F.; Rosich, L. The contributions of Paul Ehrlich to pharmacology: A tribute on the occasion of the centenary of his Nobel Prize. Pharmacology 2008, 82, 171-179.
7. Strebhardt, K.; Ullrich, A. Paul Ehrlich's magic bullet concept: 100 years of progress. Nat. Rev. Canc. 2008, 8, 473-480.
8. Moolten, F.L.; Cooperband, S.R. Selective destruction of target cells by diphtheria toxin conjugated to antibody directed against antigens on the cells. Science 1970, 169, 68-70.
9. Moolten, F.; Zajdel, S.; Cooperband, S. Immunotherapy of experimental animal tumors with antitumor antibodies conjugated to diphtheria toxin or ricin. Ann. NY Acad. Sci. 1976, 277, 690-699.
10. Pastan, I.; Hassan, R.; FitzGerald, D.J.; Kreitman, R.J. Immunotoxin treatment of cancer. Annu. Rev. Med. 2007, 58, 221-237.
11. Kreitman, R.J. Immunotoxins for targeted cancer therapy. AAPS J. 2006, 8, E532-E551.
12. Brumlik, M.J.; Daniel, B.J.; Waehler, R.; Curiel, D.T.; Giles, F.J.; Curiel, T.J. Trends in immunoconjugate and ligand-receptor based targeting development for cancer therapy. Expert Opin. Drug Deliv. 2008, 5, 87-103.
13. Potala, S.; Sahoo, S.K.; Verma, R.S. Targeted therapy of cancer using diphtheria toxin-derived immunotoxins. Drug Discov. Today 2008, 13, 807-815.
14. Fuchs, H.; Bachran, C. Targeted tumor therapies at a glance. Curr. Drug Targets 2009, 10, 89-93.
15. Kreitman, R.J. Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies. BioDrugs 2009, 23, 1-13.
16. Fracasso, G.; Stirpe, F.; Colombatti, M. Ribosome-Inactivating Protein-Containing Conjugates for Therapeutic Use. In Toxic Plant Proteins; Lord, J.M., Hartley, M.R., Eds.; Springer: Berlin/Heidelberg, Germany, 2010; Volume 18, pp. 225-263.
17. Bagel, J.; Garland, W.T.; Breneman, D.; Holick, M.; Littlejohn, T.W.; Crosby, D.; Faust, H.; Fivenson, D.; Nichols, J. Administration of DAB389IL-2 to patients with recalcitrant psoriasis: A double-blind, phase II multicenter trial. J. Am. Acad. Dermatol. 1998, 38, 938-944
18. Olsen, E.; Duvic, M.; Frankel, A.; Kim, Y.; Martin, A.; Vonderheid, E.; Jegasothy, B.; Wood, G.; Gordon, M.; Heald, P.; Oseroff, A.; Pinter-Brown, L.; Bowen, G.; Kuzel, T.; Fivenson, D.; Foss, F.; Glode, M.; Molina, A.; Knobler, E.; Stewart, S.; Cooper, K.; Stevens, S.; Craig, F.; Reuben, J.; Bacha, P.; Nichols, J. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J. Clin. Oncol. 2001, 19, 376-388.
19. Frankel, A.E.; Fleming, D.R.; Hall, P.D.; Powell, B.L.; Black, J.H.; Leftwich, C.; Gartenhaus, R. A phase II study of DT fusion protein denileukin diftitox in patients with fludarabine-refractory chronic lymphocytic leukemia. Clin. Canc. Res. 2003, 9, 3555-3561.
20. Dang, N.H.; Hagemeister, F.B.; Pro, B.; McLaughlin, P.; Romaguera, J.E.; Jones, D.; Samuels, B.; Samaniego, F.; Younes, A.; Wang, M.; Goy, A.; Rodriguez, M.A.; Walker, P.L.; Arredondo, Y.; Tong, A.T.; Fayad, L. Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma. J. Clin. Oncol. 2004, 22, 4095-4102.
21. Shaughnessy, P.J.; Bachier, C.; Grimley, M.; Freytes, C.O.; Callander, N.S.; Essell, J.H.; Flomenberg, N.; Selby, G.; Lemaistre, C.F. Denileukin diftitox for the treatment of steroid- resistant acute graft-versus-host disease. Biol. Blood Marrow Transplant. 2005, 11, 188-193.
22. Frankel, A.E.; Surendranathan, A.; Black, J.H.; White, A.; Ganjoo, K.; Cripe, L.D. Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia. Cancer 2006, 106, 2158-2164.
23. Dang, N.H.; Pro, B.; Hagemeister, F.B.; Samaniego, F.; Jones, D.; Samuels, B.I.; Rodriguez, M.A.; Goy, A.; Romaguera, J.E.; McLaughlin, P.; Tong, A.T.; Turturro, F.; Walker, P.L.; Fayad, L. Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. Br. J. Haematol. 2007, 136, 439-447.
24. Gerena-Lewis, M.; Crawford, J.; Bonomi, P.; Maddox, A.M.; Hainsworth, J.; McCune, D.E.; Shukla, R.; Zeigler, H.; Hurtubise, P.; Chowdhury, T.R.; Fletcher, B.; Dyehouse, K.; Ghalie, R.; Jazieh, A.R. A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer. Am. J. Clin. Oncol. 2009, 32, 269-273.
25. Prince, H.M.; Duvic, M.; Martin, A.; Sterry, W.; Assaf, C.; Sun, Y.; Straus, D.; Acosta, M.; Negro-Vilar, A. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J.Clin. Oncol. 2010, 28, 1870-1877.
26. LeMaistre, C.F.; Meneghetti, C.; Rosenblum, M.; Reuben, J.; Parker, K.; Shaw, J.; Deisseroth, A.; Woodworth, T.; Parkinson, D.R. Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor. Blood 1992, 79, 2547-2554.
27. Kuzel, T.M.; Rosen, S.T.; Gordon, L.I.; Winter, J.; Samuelson, E.; Kaul, K.; Roenigk, H.H.; Nylen, P.; Woodworth, T. Phase I trial of the diphtheria toxin/interleukin-2 fusion protein DAB486IL-2: Efficacy in mycosis fungoides and other non-Hodgkin's lymphomas. Leuk. Lymphoma 1993, 11, 369-377.
28. LeMaistre, C.F.; Craig, F.E.; Meneghetti, C.; McMullin, B.; Parker, K.; Reuben, J.; Boldt, D.H.; Rosenblum, M.; Woodworth, T. Phase I trial of a 90-minute infusion of the fusion toxin DAB486IL-2 in hematological cancers. Canc. Res. 1993, 53, 3930-3934
29. Platanias, L.C.; Ratain, M.J.; O'Brien, S.; Larson, R.A.; Vardiman, J.W.; Shaw, J.P.; Williams, S.F.; Baron, J.M.; Parker, K.; Woodworth, T.G. Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies. Leuk. Lymphoma 1994, 14, 257-262.
30. Tepler, I.; Schwartz, G.; Parker, K.; Charette, J.; Kadin, M.E.; Woodworth, T.G.; Schnipper, L.E. Phase I trial of an interleukin-2 fusion toxin (DAB486IL-2) in hematologic malignancies: Complete response in a patient with Hodgkin's disease refractory to chemotherapy. Cancer 1994, 73, 1276-1285.
31. Moreland, L.W.; Sewell, K.L.; Trentham, D.E.; Bucy, R.P.; Sullivan, W.F.; Schrohenloher, R.E.; Shmerling, R.H.; Parker, K.C.; Swartz, W.G.; Woodworth, T.G.; et al. Interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid arthritis. A double-blind, placebo-controlled trial with open-label extension. Arthritis Rheum. 1995, 38, 1177-1186.
32. Laske, D.W.; Youle, R.J.; Oldfield, E.H. Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat. Med. 1997, 3, 1362-1368.
33. Weaver, M.; Laske, D.W. Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107) for therapy of malignant gliomas. J. Neurooncol. 2003, 65, 3-13.
34. Debinski, W. Molecular targeting with recombinant cytotoxins for the treatment of brain tumors. Drug Dev. Res. 2008, 69, 407-414.
35. Frankel, A.E.; Powell, B.L.; Hall, P.D.; Case, L.D.; Kreitman, R.J. Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony-stimulating factor fusion protein (DT388GMCSF) for refractory or relapsed acute myeloid leukemia. Clin. Canc. Res. 2002, 8, 1004-1013.
36. Frankel, A.E.; Zuckero, S.L.; Mankin, A.A.; Grable, M.; Mitchell, K.; Lee, Y.J.; Neville, D.M.; Woo, J.H. Anti-CD3 recombinant diphtheria immunotoxin therapy of cutaneous T cell lymphoma. Curr. Drug Targets 2009, 10, 104-109.
37. Woo, J.H.; Lee, Y.J.; Neville, D.M.; Frankel, A.E. Pharmacology of anti-CD3 diphtheria immunotoxin in CD3 positive T-cell lymphoma trials. Meth. Mol. Biol. 2010, 651, 157-175.
38. Testa, U.; Riccioni, R.; Biffoni, M.; Diverio, D.; Lo-Coco, F.; Foa, R.; Peschle, C.; Frankel, A.E. Diphtheria toxin fused to variant human interleukin-3 induces cytotoxicity of blasts from patients with acute myeloid leukemia according to the level of interleukin-3 receptor expression. Blood 2005, 106, 2527-2529.
39. Pai, L.; Bookman, M.; Ozols, R.; Young, R.; Smith, J., 2d; Longo, D.; Gould, B.; Frankel, A.; McClay, E.; Howell, S. Clinical evaluation of intraperitoneal Pseudomonas exotoxin immunoconjugate OVB3-PE in patients with ovarian cancer. J. Clin. Oncol. 1991, 9, 2095-2103.
40. Pai-Scherf, L.H.; Villa, J.; Pearson, D.; Watson, T.; Liu, E.; Willingham, M.C.; Pastan, I. Hepatotoxicity in Cancer Patients Receiving erb-38, a Recombinant Immunotoxin That Targets the erbB2 Receptor. Clin. Canc. Res. 1999, 5, 2311-2315.
41. Hassan, R.; Bullock, S.; Premkumar, A.; Kreitman, R.J.; Kindler, H.; Willingham, M.C.; Pastan, I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin. Canc. Res. 2007, 13, 5144-5149.
42. Kreitman, R.J.; Hassan, R.; Fitzgerald, D.J.; Pastan, I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin. Canc. Res. 2009, 15, 5274-5279.
43. Pai, L.H.; Wittes, R.; Setser, A.; Willingham, M.C.; Pastan, I. Treatment of advanced solid tumors with immunotoxin LMB-1: An antibody linked to Pseudomonas exotoxin. Nat. Med. 1996, 2, 350-353.
44. Kreitman, R.J.; Wilson, W.H.; Bergeron, K.; Raggio, M.; Stetler-Stevenson, M.; FitzGerald, D.J.; Pastan, I. Efficacy of the Anti-CD22 Recombinant Immunotoxin BL22 in ChemotherapyResistant Hairy-Cell Leukemia. New Engl. J. Med. 2001, 345, 241-247.
45. Kreitman, R.J.; Squires, D.R.; Stetler-Stevenson, M.; Noel, P.; FitzGerald, D.J.P.; Wilson, W.H.; Pastan, I. Phase I Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With B-Cell Malignancies. J. Clin. Oncol. 2005, 23, 6719-6729.
46. Kreitman, R.J.; Stetler-Stevenson, M.; Margulies, I.; Noel, P.; FitzGerald, D.J.P.; Wilson, W.H.; Pastan, I. Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell Leukemia. J. Clin. Oncol. 2009, 27, 2983-2990.
47. Wayne, A.S.; Kreitman, R.J.; Findley, H.W.; Lew, G.; Delbrook, C.; Steinberg, S.M.; Stetler-Stevenson, M.; FitzGerald, D.J.; Pastan, I. Anti-CD22 Immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-Positive Hematologic Malignancies of Childhood: Preclinical Studies and Phase I Clinical Trial. Clin. Canc. Res. 2010, 16, 1894-1903.
48. Kreitman, R.J.; Wilson, W.H.; White, J.D.; Stetler-Stevenson, M.; Jaffe, E.S.; Giardina, S.; Waldmann, T.A.; Pastan, I. Phase I Trial of Recombinant Immunotoxin Anti-Tac(Fv)-PE38 (LMB-2) in Patients With Hematologic Malignancies. J. Clin. Oncol. 2000, 18, 1622-1636.
49. Azemar, M.; Djahansouzi, S.; Jäger, E.; Solbach, C.; Schmidt, M.; Maurer, A.B.; Mross, K.; Unger, C.; Minckwitz, G.V.; Dall, P.; Groner, B.; Wels, W.S. Regression of Cutaneous Tumor Lesions in Patients Intratumorally Injected with a Recombinant Single-chain Antibody-toxin Targeted to ErbB2/HER2. Breast Canc. Res. Treat. 2003, 82, 155-164.
50. von Minckwitz, G.; Harder, S.; Hovelmann, S.; Jager, E.; Al-Batran, S.E.; Loibl, S.; Atmaca, A.; Cimpoiasu, C.; Neumann, A.; Abera, A.; Knuth, A.; Kaufmann, M.; Jager, D.; Maurer, A.B.; Wels, W.S. Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas. Breast Canc. Res. 2005, 7, R617-R626.
51. Goldberg, M.R.; Heimbrook, D.C.; Russo, P.; Sarosdy, M.F.; Greenberg, R.E.; Giantonio, B.J.; Linehan, W.M.; Walther, M.; Fisher, H.A.; Messing, E.; et al. Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer. Clin. Canc. Res. 1995, 1, 57-61.
52. Sampson, J.H.; Akabani, G.; Archer, G.E.; Bigner, D.D.; Berger, M.S.; Friedman, A.H.; Friedman, H.S.; Herndon, J.E., 2nd; Kunwar, S.; Marcus, S.; McLendon, R.E.; Paolino, A.; Penne, K.; Provenzale, J.; Quinn, J.; Reardon, D.A.; Rich, J.; Stenzel, T.; Tourt-Uhlig, S.; Wikstrand, C.; Wong, T.; Williams, R.; Yuan, F.; Zalutsky, M.R.; Pastan, I. Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors. J. Neurooncol. 2003, 65, 27-35.
53. Sampson, J.H.; Reardon, D.A.; Friedman, A.H.; Friedman, H.S.; Coleman, R.E.; McLendon, R.E.; Pastan, I.; Bigner, D.D. Sustained radiographic and clinical response in patient with bifrontalrecurrent glioblastoma multiforme with intracerebral infusion of therecombinant targeted toxin TP-38: Case study. Neuro. Oncol. 2005, 7, 90-96.
54. Sampson, J.H.; Akabani, G.; Archer, G.E.; Berger, M.S.; Coleman, R.E.; Friedman, A.H.; Friedman, H.S.; Greer, K.; Herndon, J.E., 2nd; Kunwar, S.; McLendon, R.E.; Paolino, A.; Petry, N.A.; Provenzale, J.M.; Reardon, D.A.; Wong, T.Z.; Zalutsky, M.R.; Pastan, I.; Bigner, D.D. Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors. Neuro. Oncol. 2008, 10, 320-329.
55. Posey, J.A.; Khazaeli, M.B.; Bookman, M.A.; Nowrouzi, A.; Grizzle, W.E.; Thornton, J.; Carey, D.E.; Lorenz, J.M.; Sing, A.P.; Siegall, C.B.; LoBuglio, A.F.; Saleh, M.N. A Phase I Trial of the Single-Chain Immunotoxin SGN-10 (BR96 sFv-PE40) in Patients with Advanced Solid Tumors. Clin. Canc. Res. 2002, 8, 3092-3099.
56. Weber, F.; Asher, A.; Bucholz, R.; Berger, M.; Prados, M.; Chang, S.; Bruce, J.; Hall, W.; Rainov, N.G.; Westphal, M.; Warnick, R.E.; Rand, R.W.; Floeth, F.; Rommel, F.; Pan, H.; Hingorani, V.N.; Puri, R.K. Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J. Neurooncol. 2003, 64, 125-137.
57. Weber, F.W.; Floeth, F.; Asher, A.; Bucholz, R.; Berger, M.; Prados, M.; Chang, S.; Bruce, J.; Hall, W.; Rainov, N.G.; Westphal, M.; Warnick, R.E.; Rand, R.W.; Rommell, F.; Pan, H.; Hingorani, V.N.; Puri, R.K. Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma. Acta Neurochir. Suppl. 2003, 88, 93-103.
58. Garland, L.; Gitlitz, B.; Ebbinghaus, S.; Pan, H.; de Haan, H.; Puri, R.K.; Von Hoff, D.; Figlin, R. Phase I trial of intravenous IL-4 pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor. J. Immunother. 2005, 28, 376-381.
59. Kreitman, R.J.; Tallman, M.S.; Coutre, S.E.; Robak, T.; Wilson, W.H.; Stetler-Stevenson, M.; Noel, P.; FitzGerald, D.J.; McDevitt, J.T.; Pastan, I. Phase I trial of recombinant immunotoxin CAT-8015 (HA22) in multiply relapsed hairy cell leukemia. J. Clin. Oncol. 2010, 28, 6523.
60. Mussai, F.; Campana, D.; Bhojwani, D.; Stetler-Stevenson, M.; Steinberg, S.M.; Wayne, A.S.; Pastan, I. Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia. Br. J. Haematol. 2010, 150, 352-358.
61. Kunwar, S. Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: Presentation of interim findings from ongoing phase 1 studies. Acta Neurochir. Suppl. 2003, 88, 105-111.
62. Parney, I.F.; Kunwar, S.; McDermott, M.; Berger, M.; Prados, M.; Cha, S.; Croteau, D.; Puri, R.K.; Chang, S.M. Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma. J. Neurosurg. 2005, 102, 267-275.
63. Kunwar, S.; Prados, M.D.; Chang, S.M.; Berger, M.S.; Lang, F.F.; Piepmeier, J.M.; Sampson, J.H.; Ram, Z.; Gutin, P.H.; Gibbons, R.D.; Aldape, K.D.; Croteau, D.J.; Sherman, J.W.; Puri, R.K. Direct Intracerebral Delivery of Cintredekin Besudotox (IL13-PE38QQR) in Recurrent Malignant Glioma: A Report by the Cintredekin Besudotox Intraparenchymal Study Group. J. Clin. Oncol. 2007, 25, 837-844.
64. Kunwar, S.; Chang, S.; Westphal, M.; Vogelbaum, M.; Sampson, J.; Barnett, G.; Shaffrey, M.; Ram, Z.; Piepmeier, J.; Prados, M.; Croteau, D.; Pedain, C.; Leland, P.; Husain, S.R.; Joshi, B.H.; Puri, R.K.; for the PRECISE Study Group Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro. Oncol. 2010, 12, 871-881.
65. Vitetta, E.S.; Stone, M.; Amlot, P.; Fay, J.; May, R.; Till, M.; Newman, J.; Clark, P.; Collins, R.; Cunningham, D.; Ghetie, V.; Uhr, J.W.; Thorpe, P.E. Phase I Immunotoxin Trial in Patients with B-Cell Lymphoma. Canc. Res. 1991, 51, 4052-4058.
66. Amlot, P.; Stone, M.; Cunningham, D.; Fay, J.; Newman, J.; Collins, R.; May, R.; McCarthy, M.; Richardson, J.; Ghetie, V. A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. Blood 1993, 82, 2624-2633.
67. Sausville, E.A.; Headlee, D.; Stetler-Stevenson, M.; Jaffe, E.S.; Solomon, D.; Figg, W.D.; Herdt, J.; Kopp, W.C.; Rager, H.; Steinberg, S.M.; et al. Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: A phase I study. Blood 1995, 85, 3457-3465.
68. Conry, R.M.; Khazaeli, M.B.; Saleh, M.N.; Ghetie, V.; Vitetta, E.S.; Liu, T.; LoBuglio, A.F. Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma: Effect of an intensive schedule of administration. J. Immunother. Emphasis Tumor Immunol. 1995, 18, 231-241.
69. Stone, M.J.; Sausville, E.A.; Fay, J.W.; Headlee, D.; Collins, R.H.; Figg, W.D.; Stetler-Stevenson, M.; Jain, V.; Jaffe, E.S.; Solomon, D.; Lush, R.M.; Senderowicz, A.; Ghetie, V.; Schindler, J.; Uhr, J.W.; Vitetta, E.S. A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma. Blood 1996, 88, 1188-1197.
70. Messmann, R.A.; Vitetta, E.S.; Headlee, D.; Senderowicz, A.M.; Figg, W.D.; Schindler, J.; Michiel, D.F.; Creekmore, S.; Steinberg, S.M.; Kohler, D.; Jaffe, E.S.; Stetler-Stevenson, M.; Chen, H.; Ghetie, V.; Sausville, E.A. A Phase I Study of Combination Therapy with Immunotoxins IgG-HD37-Deglycosylated Ricin A Chain (dgA) and IgG-RFB4-dgA (Combotox) in Patients with Refractory CD19(+), CD22(+) B Cell Lymphoma. Clin. Canc. Res. 2000, 6, 1302-1313.
71. Herrera, L.; Bostrom, B.; Gore, L.; Sandler, E.; Lew, G.; Schlegel, P.G.; Aquino, V.; Ghetie, V.; Vitetta, E.S.; Schindler, J. A phase 1 study of Combotox in pediatric patients with refractory B-lineage acute lymphoblastic leukemia. J. Pediatr. Hematol. Oncol. 2009, 31, 936-941.
72. Engert, A.; Diehl, V.; Schnell, R.; Radszuhn, A.; Hatwig, M.T.; Drillich, S.; Schon, G.; Bohlen, H.; Tesch, H.; Hansmann, M.L.; Barth, S.; Schindler, J.; Ghetie, V.; Uhr, J.; Vitetta, E. A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. Blood 1997, 89, 403-410
73. Schnell, R.; Vitetta, E.; Schindler, J.; Barth, S.; Winkler, U.; Borchmann, P.; Hansmann, M.L.; Diehl, V.; Ghetie, V.; Engert, A. Clinical trials with an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin's lymphoma. Leuk. Lymphoma 1998, 30, 525-537.
74. Schnell, R.; Vitetta, E.; Schindler, J.; Borchmann, P.; Barth, S.; Ghetie, V.; Hell, K.; Drillich, S.; Diehl, V.; Engert, A. Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin. Leukemia 2000, 14, 129-135.
75. Schnell, R.; Borchmann, P.; Staak, J.O.; Schindler, J.; Ghetie, V.; Vitetta, E.S.; Engert, A. Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma. Ann. Oncol. 2003, 14, 729-736.
76. Martin, P.J.; Pei, J.; Gooley, T.; Anasetti, C.; Appelbaum, F.R.; Deeg, J.; Hansen, J.A.; Nash, R.A.; Petersdorf, E.W.; Storb, R.; Ghetie, V.; Schindler, J.; Vitetta, E.S. Evaluation of a CD25- specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation. Biol. Blood Marrow Transplant. 2004, 10, 552-560.
77. Schnell, R.; Staak, O.; Borchmann, P.; Schwartz, C.; Matthey, B.r.; Hansen, H.; Schindler, J.; Ghetie, V.; Vitetta, E.S.; Diehl, V.; Engert, A. A Phase I Study with an Anti-CD30 Ricin A-Chain Immunotoxin (Ki-4.dgA) in Patients with Refractory CD30+ Hodgkin's and Non-Hodgkin's Lymphoma. Clin. Canc. Res. 2002, 8, 1779-1786.
78. Grossbard, M.L.; Gribben, J.G.; Freedman, A.S.; Lambert, J.M.; Kinsella, J.; Rabinowe, S.N.; Eliseo, L.; Taylor, J.A.; Blattler, W.A.; Epstein, C.L.; et al. Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma. Blood 1993, 81, 2263-2271.
79. Grossbard, M.L.; Lambert, J.M.; Goldmacher, V.S.; Spector, N.L.; Kinsella, J.; Eliseo, L.; Coral, F.; Taylor, J.A.; Blattler, W.A.; Epstein, C.L.; et al. Anti-B4-blocked ricin: A phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J. Clin. Oncol. 1993, 11, 726-737.
80. Multani, P.S.; O'Day, S.; Nadler, L.M.; Grossbard, M.L. Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma. Clin. Canc. Res. 1998, 4, 2599-2604.
81. ™s Lymphoma. Clin. Canc. Res. 1999, 5, 2392-2398.
82. Zalcberg, J.R.; Pietersz, G.; Toohey, B.; Laird, J.; Huggins, R.; Zimet, A.S.; Hennessy, O.; McKenzie, A.; McKenzie, I.F.C. A phase study of the intralesional injection of ricin-monoclonal antibody conjugates in patients with hepatic metastases. Eur. J. Canc. 1994, 30, 1227-1231.
83. Lynch, T.J., Jr. Immunotoxin therapy of small-cell lung cancer. N901-blocked ricin for relapsed small-cell lung cancer. Chest 1993, 103, 436S-439S.
84. Epstein, C.; Lynch, T.; Shefner, J.; Wen, P.; Maxted, D.; Braman, V.; Ariniello, P.; Coral, F.; Ritz, J. Use of the immunotoxin N901-blocked ricin in patients with small-cell lung cancer. Int. J. Canc. Suppl. 1994, 8, 57-59
85. Lynch, T., Jr; Lambert, J.; Coral, F.; Shefner, J.; Wen, P.; Blattler, W.; Collinson, A.; Ariniello, P.; Braman, G.; Cook, S.; Esseltine, D.; Elias, A.; Skarin, A.; Ritz, J. Immunotoxin therapy of small-cell lung cancer: A phase I study of N901- blocked ricin. J. Clin. Oncol. 1997, 15, 723-734.
86. Frankel, A.E.; Laver, J.H.; Willingham, M.C.; Burns, L.J.; Kersey, J.H.; Vallera, D.A. Therapy of Patients with T-cell Lymphomas and Leukemias Using an Anti-CD7 Monoclonal AntibodyRich a Chain Immunotoxin. Leuk. Lymphoma 1997, 26, 287-298.
87. van Oosterhout, Y.V.J.M.; van Emst, L.; Schattenberg, A.V.M.B.; Tax, W.J.M.; Ruiter, D.J.; Spits, H.; Nagengast, F.M.; Masereeuw, R.; Evers, S.; de Witte, T.; Preijers, F.W.M.B. A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease. Blood 2000, 95, 3693-3701.
88. Skyler, J.S.; Lorenz, T.J.; Schwartz, S.; Eisenbarth, G.S.; Einhorn, D.; Palmer, J.P.; Marks, J.B.; Greenbaum, C.; Saria, E.A.; Byers, V. Effects of an anti-CD5 immunoconjugate (CD5-plus) in recent onset type I diabetes mellitus: A preliminary investigation. The CD5 Diabetes Project Team. J. Diabetes Complicat. 1993, 7, 224-232.
89. Strand, V.; Lipsky, P.E.; Cannon, G.W.; Calabrese, L.H.; Wiesenhutter, C.; Cohen, S.B.; Olsen, N.J.; Lee, M.L.; Lorenz, T.J.; Nelson, B. Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Results of two phase II studies. The CD5 Plus Rheumatoid Arthritis Investigators Group. Arthritis Rheum. 1993, 36, 620-630.
90. Fishwild, D.M.; Strand, V. Administration of an anti-CD5 immunoconjugate to patients with rheumatoid arthritis: Effect on peripheral blood mononuclear cells and in vitro immune function. J. Rheumatol. 1994, 21, 596-604.
91. Stafford, F.J.; Fleisher, T.A.; Lee, G.; Brown, M.; Strand, V.; Austin, H.A., 3rd; Balow, J.E.; Klippel, J.H. A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus. J. Rheumatol. 1994, 21, 2068-2070.
92. Olsen, N.J.; Brooks, R.H.; Cush, J.J.; Lipsky, P.E.; St Clair, E.W.; Matteson, E.L.; Gold, K.N.; Cannon, G.W.; Jackson, C.G.; McCune, W.J.; Fox, D.A.; Nelson, B.; Lorenz, T.; Strand, V. A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheumatoid arthritis. The Xoma RA Investigator Group. Arthritis Rheum. 1996, 39, 1102-1108.
93. Kernan, N.A.; Byers, V.; Scannon, P.J.; Mischak, R.P.; Brochstein, J.; Flomenberg, N.; Dupont, B.; O'Reilly, R.J. Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin. JAMA 1988, 259, 3154-3157.
94. Byers, V.; Henslee, P.; Kernan, N.; Blazar, B.; Gingrich, R.; Phillips, G.; LeMaistre, C.; Gilliland, G.; Antin, J.; Martin, P. Use of an anti-pan T-lymphocyte ricin a chain immunotoxin in steroid- resistant acute graft-versus-host disease. Blood 1990, 75, 1426-1432.
95. LeMaistre, C.; Rosen, S.; Frankel, A.; Kornfeld, S.; Saria, E.; Meneghetti, C.; Drajesk, J.; Fishwild, D.; Scannon, P.; Byers, V. Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T- cell lymphoma. Blood 1991, 78, 1173-1182.
96. Laurent, G.; Pris, J.; Farcet, J.; Carayon, P.; Blythman, H.; Casellas, P.; Poncelet, P.; Jansen, F. Effects of therapy with T101 ricin A-chain immunotoxin in two leukemia patients. Blood 1986, 67, 1680-1687
97. Hertler, A.A.; Schlossman, D.M.; Borowitz, M.J.; Laurent, G.; Jansen, F.K.; Schmidt, C.; Frankel, A.E. A phase I study of T101-ricin A chain immunotoxin in refractory chronic lymphocytic leukemia. J. Biol. Respon. Mod. 1988, 7, 97-113.
98. Hertler, A.A.; Schlossman, D.M.; Borowitz, M.J.; Blythman, H.E.; Casellas, P.; Frankel, A.E. An anti-CD5 immunotoxin for chronic lymphocytic leukemia: Enhancement of cytotoxicity with human serum albumin-monensin. Int. J. Canc. 1989, 43, 215-219.
99. Castillo, E. MDX-RA Medarex Inc. IDrugs 1998, 1, 476-479.
100. Clark, D.S.; Emery, J.M.; Munsell, M.F. Inhibition of posterior capsule opacification with an immunotoxin specific for lens epithelial cells: 24 month clinical results. J. Cataract Refract. Surg. 1998, 24, 1614-1620.
101. Meacock, W.R.; Spalton, D.J.; Hollick, E.J.; Boyce, J.F.; Barman, S.; Sanguinetti, G. Double- masked prospective ocular safety study of a lens epithelial cell antibody to prevent posterior capsule opacification. J. Cataract Refract. Surg. 2000, 26, 716-721.
102. Hertler, A.A.; Spitler, L.E.; Frankel, A.E. Humoral immune response to a ricin A chain immunotoxin in patients with metastatic melanoma. Canc. Drug Deliv. 1987, 4, 245-253.
103. Spitler, L.E.; del Rio, M.; Khentigan, A.; Wedel, N.I.; Brophy, N.A.; Miller, L.L.; Harkonen, W.S.; Rosendorf, L.L.; Lee, H.M.; Mischak, R.P.; et al. Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Canc. Res. 1987, 47, 1717-1723.
104. Mischak, R.P.; Foxall, C.; Rosendorf, L.L.; Knebel, K.; Scannon, P.J.; Spitler, L.E. Human antibody responses to components of the monoclonal antimelanoma antibody ricin A chain immunotoxin XomaZyme-MEL. Mol. Biother. 1990, 2, 104-109.
105. Oratz, R.; Speyer, J.L.; Wernz, J.C.; Hochster, H.; Meyers, M.; Mischak, R.; Spitler, L.E. Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: Results of a phase II trial. J. Biol. Response Mod. 1990, 9, 345-354.
106. Gonzalez, R.; Salem, P.; Bunn, P.A., Jr.; Zukiwski, A.A.; Lamb, R.; Benjamin, R.S.; Spitler, L.; Wedel, N.; Robinson, W.A. Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: A phase I trial. Mol. Biother. 1991, 3, 192-196.
107. Selvaggi, K.; Saria, E.A.; Schwartz, R.; Vlock, D.R.; Ackerman, S.; Wedel, N.; Kirkwood, J.M.; Jones, H.; Ernstoff, M.S. Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma. J. Immunother. Emphasis Tumor Immunol. 1993, 13, 201-207.
108. Byers, V.S.; Rodvien, R.; Grant, K.; Durrant, L.G.; Hudson, K.H.; Baldwin, R.W.; Scannon, P.J. Phase I study of monoclonal antibody-ricin A chain immunotoxin XomaZyme-791 in patients with metastatic colon cancer. Canc. Res. 1989, 49, 6153-6160.
109. Durrant, L.G.; Byers, V.S.; Scannon, P.J.; Rodvien, R.; Grant, K.; Robins, R.A.; Marksman, R.A.; Baldwin, R.W. Humoral immune responses to XMMCO-791-RTA immunotoxin in colorectal cancer patients. Clin. Exp. Immunol. 1989, 75, 258-264.
110. LoRusso, P.M.; Lomen, P.L.; Redman, B.G.; Poplin, E.; Bander, J.J.; Valdivieso, M. Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. Am. J. Clin. Oncol. 1995, 18, 307-312.
111. Laske, D.W.; Muraszko, K.M.; Oldfield, E.H.; DeVroom, H.L.; Sung, C.; Dedrick, R.L.; Simon, T.R.; Colandrea, J.; Copeland, C.; Katz, D.; Greenfield, L.; Groves, E.S.; Houston, L.L.; Youle, R.J. Intraventricular immunotoxin therapy for leptomeningeal neoplasia. Neurosurgery 1997, 41, 1039-1049, 1049-1051.
112. Gould, B.J.; Borowitz, M.J.; Groves, E.S.; Carter, P.W.; Anthony, D.; Weiner, L.M.; Frankel, A.E. Phase I study of an anti-breast cancer immunotoxin by continuous infusion: Report of a targeted toxic effect not predicted by animal studies. J. Natl. Canc. Inst. 1989, 81, 775-781.
113. Weiner, L.M.; O'Dwyer, J.; Kitson, J.; Comis, R.L.; Frankel, A.E.; Bauer, R.J.; Konrad, M.S.; Groves, E.S. Phase I evaluation of an anti-breast carcinoma monoclonal antibody 260F9-recombinant ricin A chain immunoconjugate. Canc. Res. 1989, 49, 4062-4067.
114. Uckun, F.M. Immunotoxins for the treatment of leukaemia. Br. J. Haematol. 1993, 85, 435-438.
115. Uckun, F.M.; Bellomy, K.; O'Neill, K.; Messinger, Y.; Johnson, T.; Chen, C.-L. Toxicity, Biological Activity, and Pharmacokinetics of TXU (Anti-CD7)-Pokeweed Antiviral Protein in Chimpanzees and Adult Patients Infected with Human Immunodeficiency Virus. J. Pharmacol. Exp. Therapeut. 1999, 291, 1301-1307.
116. Falini, B.; Flenghi, L.; Aversa, F.; Barbabietola, G.; Martelli, M.F.; Comeli, P.; Tazzari, P.L.; Broe, M.K.; Stein, H.; Dürkop, H.; Pizzolo, G.; Bolognesi, A.; Stirpe, F.; Sabattini, E.; Pileri, S. Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin. The Lancet 1992, 339, 1195-1196.
117. Dean, A.; Talpaz, M.; Kantarjian, H.; Faderl, S.; Jabbour, E.; Ravandi Kashani, F.; O'Brien, S.M.; Rosenblum, M.; Cortes, J.E. Phase I clinical trial of the anti-CD33 immunotoxin HuM195/rgel in patients (pts) with advanced myeloid malignancies. J. Clin. Oncol. 2010, 28, 6549.
118. Yu, L.; Gu, F.; Zhang, C.; Xie, S.; Guo, Y. Targeted diagnosis and treatment of superficial bladder cancer with monoclonal antibody BDI-1. Chin. Med. J. (Engl.) 1998, 111, 404-407.
119. Menestrina, G.; Schiavo, G.; Montecucco, C. Molecular mechanisms of action of bacterial protein toxins. Mol. Aspect. Med. 1994, 15, 79-193.
120. Falnes, P.O.; Sandvig, K. Penetration of protein toxins into cells. Curr. Opin. Cell Biol. 2000, 12, 407-413.
121. Choe, S.; Bennett, M.J.; Fujii, G.; Curmi, P.M.; Kantardjieff, K.A.; Collier, R.J.; Eisenberg, D. The crystal structure of diphtheria toxin. Nature 1992, 357, 216-222.
122. Tsuneoka, M.; Nakayama, K.; Hatsuzawa, K.; Komada, M.; Kitamura, N.; Mekada, E. Evidence for involvement of furin in cleavage and activation of diphtheria toxin. J. Biol. Chem. 1993, 268, 26461-26465.
123. Chiron, M.F.; Fryling, C.M.; FitzGerald, D.J. Cleavage of pseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver. J. Biol. Chem. 1994, 269, 18167-18176.
124. Donovan, J.J.; Simon, M.I.; Draper, R.K.; Montal, M. Diphtheria toxin forms transmembrane channels in planar lipid bilayers. Proc. Natl. Acad. Sci. USA 1981, 78, 172-176.
125. Kagan, B.L.; Finkelstein, A.; Colombini, M. Diphtheria toxin fragment forms large pores in phospholipid bilayer membranes. Proc. Natl. Acad. Sci. USA 1981, 78, 4950-4954.
126. Lemichez, E.; Bomsel, M.; Devilliers, G.; vander Spek, J.; Murphy, J.R.; Lukianov, E.V.; Olsnes, S.; Boquet, P. Membrane translocation of diphtheria toxin fragment A exploits early to late endosome trafficking machinery. Mol. Microbiol. 1997, 23, 445-457.
127. Ratts, R.; Zeng, H.; Berg, E.A.; Blue, C.; McComb, M.E.; Costello, C.E.; vanderSpek, J.C.; Murphy, J.R. The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex. J. Cell Biol. 2003, 160, 1139-1150.
128. Trujillo, C.; Ratts, R.; Tamayo, A.; Harrison, R.; Murphy, J.R. Trojan horse or proton force: Finding the right partner(s) for toxin translocation. Neurotox. Res. 2006, 9, 63-71.
129. Trujillo, C.; Taylor-Parker, J.; Harrison, R.; Murphy, J.R. Essential lysine residues within transmembrane helix 1 of diphtheria toxin facilitate COPI binding and catalytic domain entry. Mol. Microbiol. 2010, 76, 1010-1019.
130. Morimoto, H.; Bonavida, B. Diphtheria toxin- and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-alpha. J. Immunol. 1992, 149, 2089-2094.
131. Thorburn, J.; Frankel, A.E.; Thorburn, A. Apoptosis by leukemia cell-targeted diphtheria toxin occurs via receptor-independent activation of Fas-associated death domain protein. Clin. Canc. Res. 2003, 9, 861-865.
132. Thorburn, A.; Thorburn, J.; Frankel, A.E. Induction of apoptosis by tumor cell-targeted toxins. Apoptosis 2004, 9, 19-25.
133. Deng, Q.; Barbieri, J.T. Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins. Annu. Rev. Microbiol. 2008, 62, 271-288.
134. Yamaizumi, M.; Mekada, E.; Uchida, T.; Okada, Y. One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell 1978, 15, 245-250.
135. Strauchen, J.A.; Breakstone, B.A. IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases. Am. J. Pathol. 1987, 126, 506-512.
136. Strauchen, J.A. Interleukin receptors in lymphoid lesions. Relevance to diagnosis, biology, and therapy. Pathol. Annu. 1989, 24, 149-165.
137. Kodaka, T.; Uchiyama, T.; Ishikawa, T.; Kamio, M.; Onishi, R.; Itoh, K.; Hori, T.; Uchino, H.; Tsudo, M.; Araki, K. Interleukin-2 receptor beta-chain (p70-75) expressed on leukemic cells from adult T cell leukemia patients. Jpn. J. Canc. Res. 1990, 81, 902-908.
138. Yagura, H.; Tamaki, T.; Furitsu, T.; Tomiyama, Y.; Nishiura, T.; Tominaga, N.; Katagiri, S.; Yonezawa, T.; Tarui, S. Demonstration of high-affinity interleukin-2 receptors on B-chronic lymphocytic leukemia cells: Functional and structural characterization. Blut 1990, 60, 181-186.
139. Re, G.G.; Waters, C.; Poisson, L.; Willingham, M.C.; Sugamura, K.; Frankel, A.E. Interleukin 2 (IL-2) receptor expression and sensitivity to diphteria fusion toxin DAB389IL-2 in cultured hematopoietic cells. Canc. Res. 1996, 56, 2590-2595.
140. Williams, D.P.; Snider, C.E.; Strom, T.B.; Murphy, J.R. Structure/function analysis of interleukin-2-toxin (DAB486-IL-2). Fragment B sequences required for the delivery of fragment A to the cytosol of target cells. J. Biol. Chem. 1990, 265, 11885-11889.
141. LeMaistre, C.F.; Saleh, M.N.; Kuzel, T.M.; Foss, F.; Platanias, L.C.; Schwartz, G.; Ratain, M.; Rook, A.; Freytes, C.O.; Craig, F.; Reuben, J.; Nichols, J.C. Phase I trial of a ligand fusion- protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood 1998, 91, 399-405.
142. McGinnis, K.S.; Shapiro, M.; Junkins-Hopkins, J.M.; Smith, M.; Lessin, S.R.; Vittorio, C.C.; Rook, A.H. Denileukin diftitox for the treatment of panniculitic lymphoma. Arch. Dermatol. 2002, 138, 740-742.
143. Martin, A.; Gutierrez, E.; Muglia, J.; McDonald, C.J.; Guzzo, C.; Gottlieb, A.; Pappert, A.; Garland, W.T.; Bagel, J.; Bacha, P. A multicenter dose-escalation trial with denileukin diftitox (ONTAK, DAB(389)IL-2) in patients with severe psoriasis. J. Am. Acad. Dermatol. 2001, 45, 871-881.
144. Kelleher, C.A.; Wong, G.G.; Clark, S.C.; Schendel, P.F.; Minden, M.D.; McCulloch, E.A. Binding of iodinated recombinant human GM-CSF to the blast cells of acute myeloblastic leukemia. Leukemia 1988, 2, 211-215.
145. Frankel, A.E.; Hall, P.D.; Burbage, C.; Vesely, J.; Willingham, M.; Bhalla, K.; Kreitman, R.J. Modulation of the apoptotic response of human myeloid leukemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein. Blood 1997, 90, 3654-3661.
146. Kreitman, R.J.; Pastan, I. Recombinant toxins containing human granulocyte-macrophage colony-stimulating factor and either pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukemia cells. Blood 1997, 90, 252-259.
147. Recht, L.; Torres, C.O.; Smith, T.W.; Raso, V.; Griffin, T.W. Transferrin receptor in normal and neoplastic brain tissue: Implications for brain-tumor immunotherapy. J. Neurosurg. 1990, 72, 941-945.
148. Greenfield, L.; Johnson, V.G.; Youle, R.J. Mutations in diphtheria toxin separate binding from entry and amplify immunotoxin selectivity. Science 1987, 238, 536-539.
149. Johnson, V.G.; Wrobel, C.; Wilson, D.; Zovickian, J.; Greenfield, L.; Oldfield, E.H.; Youle, R. Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia. J. Neurosurg. 1989, 70, 240-248.
150. Liu, P.V. Extracellular toxins of Pseudomonas aeruginosa. J. Infect. Dis. 1974, 130, S94-S99.
151. Iglewski, B.H.; Kabat, D. NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin. Proc. Natl. Acad. Sci. USA 1975, 72, 2284-2288.
152. Hwang, J.; Fitzgerald, D.J.; Adhya, S.; Pastan, I. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell 1987, 48, 129-136.
153. Siegall, C.B.; Chaudhary, V.K.; FitzGerald, D.J.; Pastan, I. Functional analysis of domains II, Ib, and III of Pseudomonas exotoxin. J. Biol. Chem. 1989, 264, 14256-14261.
154. Hessler, J.L.; Kreitman, R.J. An early step in Pseudomonas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor. Biochemistry 1997, 36, 14577-14582.
155. Kounnas, M.Z.; Morris, R.E.; Thompson, M.R.; FitzGerald, D.J.; Strickland, D.K.; Saelinger, C.B. The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. J. Biol. Chem. 1992, 267, 12420-12423.
156. Smith, D.C.; Spooner, R.A.; Watson, P.D.; Murray, J.L.; Hodge, T.W.; Amessou, M.; Johannes, L.; Lord, J.M.; Roberts, L.M. Internalized Pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum. Traffic 2006, 7, 379-393.
157. Fryling, C.; Ogata, M.; FitzGerald, D. Characterization of a cellular protease that cleaves Pseudomonas exotoxin. Infect. Immun. 1992, 60, 497-502
158. Ogata, M.; Fryling, C.M.; Pastan, I.; Fitz Gerald, D.J. Cell-mediated cleavage of Pseudomonas exotoxin between Arg279 and Gly280 generates the enzymatically active fragment which translocates to the cytosol. J. Biol. Chem. 1992, 267, 25396-25401.
159. McKee, M.L.; FitzGerald, D.J. Reduction of furin-nicked Pseudomonas exotoxin A: An unfolding story. Biochemistry 1999, 38, 16507-16513.
160. Lombardi, D.; Soldati, T.; Riederer, M.A.; Goda, Y.; Zerial, M.; Pfeffer, S.R. Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J. 1993, 12, 677-682.
161. Chaudhary, V.K.; Jinno, Y.; FitzGerald, D.; Pastan, I. Pseudomonas exotoxin contains a specific sequence at the carboxyl terminus that is required for cytotoxicity. Proc. Natl. Acad. Sci. USA 1990, 87, 308-312.
162. Kreitman, R.J.; Pastan, I. Importance of the glutamate residue of KDEL in increasing the cytotoxicity of Pseudomonas exotoxin derivatives and for increased binding to the KDEL receptor. Biochem. J. 1995, 307, 29-37.
163. Jackson, M.E.; Simpson, J.C.; Girod, A.; Pepperkok, R.; Roberts, L.M.; Lord, J.M. The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum. J. Cell. Sci. 1999, 112, 467-475.
164. Ogata, M.; Chaudhary, V.K.; Pastan, I.; FitzGerald, D.J. Processing of Pseudomonas exotoxin by a cellular protease results in the generation of a 37,000-Da toxin fragment that is translocated to the cytosol. J. Bio.l Chem. 1990, 265, 20678-20685.
165. Theuer, C.P.; Buchner, J.; FitzGerald, D.; Pastan, I. The N-terminal region of the 37-kDa translocated fragment of Pseudomonas exotoxin A aborts translocation by promoting its own export after microsomal membrane insertion. Proc. Natl. Acad. Sci. USA 1993, 90, 7774-7778.
166. Theuer, C.; Kasturi, S.; Pastan, I. Domain II of Pseudomonas exotoxin A arrests the transfer of translocating nascent chains into mammalian microsomes. Biochemistry 1994, 33, 5894-5900.
167. Hazes, B.; Read, R.J. Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry 1997, 36, 11051-11054.
168. Koopmann, J.O.; Albring, J.; Huter, E.; Bulbuc, N.; Spee, P.; Neefjes, J.; Hammerling, G.J.; Momburg, F. Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Sec61p channel. Immunity 2000, 13, 117-127.
169. Spooner, R.A.; Smith, D.C.; Easton, A.J.; Roberts, L.M.; Lord, J.M. Retrograde transport pathways utilised by viruses and protein toxins. Virol. J. 2006, 3, 26.
170. Iglewski, B.H.; Liu, P.V.; Kabat, D. Mechanism of action of Pseudomonas aeruginosa exotoxin Aiadenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo. Infect. Immun. 1977, 15, 138-144.
171. Carroll, S.F.; Collier, R.J. Active site of Pseudomonas aeruginosa exotoxin A. Glutamic acid 553 is photolabeled by NAD and shows functional homology with glutamic acid 148 of diphtheria toxin. J. Biol. Chem. 1987, 262, 8707-8711.
172. Jenkins, C.E.; Swiatoniowski, A.; Issekutz, A.C.; Lin, T.J. Pseudomonas aeruginosa exotoxin A induces human mast cell apoptosis by a caspase-8 and -3-dependent mechanism. J. Biol. Chem. 2004, 279, 37201-37207.
173. Wolf, P.; Elsasser-Beile, U. Pseudomonas exotoxin A: From virulence factor to anti-cancer agent. Int. J. Med. Microbiol. 2009, 299, 161-176.
174. Uchiyama, T.; Broder, S.; Waldmann, T.A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J. Immunol. 1981, 126, 1393-1397.
175. Uchiyama, T.; Nelson, D.L.; Fleisher, T.A.; Waldmann, T.A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. J. Immunol. 1981, 126, 1398-1403.
176. Waldmann, T.A. Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: A 25-year personal odyssey. J. Clin. Immunol. 2007, 27, 1-18.
177. Kreitman, R.J.; Bailon, P.; Chaudhary, V.K.; FitzGerald, D.J.; Pastan, I. Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma. Blood 1994, 83, 426-434.
178. Kreitman, R.J.; Pastan, I. Accumulation of a recombinant immunotoxin in a tumor in vivo: Fewer than 1000 molecules per cell are sufficient for complete responses. Canc. Res. 1998, 58, 968-975.
179. Robbins, D.H.; Margulies, I.; Stetler-Stevenson, M.; Kreitman, R.J. Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2). Clin Canc. Res. 2000, 6, 693-700.
180. Onda, M.; Kreitman, R.J.; Vasmatzis, G.; Lee, B.; Pastan, I. Reduction of the nonspecific animal toxicity of anti-Tac(Fv)-PE38 by mutations in the framework regions of the Fv which lower the isoelectric point. J. Immunol. 1999, 163, 6072-6077.
181. Kreitman, R.J. Recombinant immunotoxins for the treatment of haematological malignancies. Expert Opin. Biol. Ther. 2004, 4, 1115-1128.
182. Onda, M.; Willingham, M.; Wang, Q.C.; Kreitman, R.J.; Tsutsumi, Y.; Nagata, S.; Pastan, I. Inhibition of TNF-alpha produced by Kupffer cells protects against the nonspecific liver toxicity of immunotoxin anti-Tac(Fv)-PE38, LMB-2. J. Immunol. 2000, 165, 7150-7156.
183. Chakraborty, N.G.; Chattopadhyay, S.; Mehrotra, S.; Chhabra, A.; Mukherji, B. Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma. Hum. Immunol. 2004, 65, 794-802.
184. Powell, D.J., Jr.; Felipe-Silva, A.; Merino, M.J.; Ahmadzadeh, M.; Allen, T.; Levy, C.; White, D.E.; Mavroukakis, S.; Kreitman, R.J.; Rosenberg, S.A.; Pastan, I. Administration of a CD25- directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo. J. Immunol. 2007, 179, 4919-4928.
185. Clark, E.A. CD22, a B cell-specific receptor, mediates adhesion and signal transduction. J. Immunol. 1993, 150, 4715-4718.
186. Robbins, B.A.; Ellison, D.J.; Spinosa, J.C.; Carey, C.A.; Lukes, R.J.; Poppema, S.; Saven, A.; Piro, L.D. Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia. Blood 1993, 82, 1277-1287.
187. Gudowius, S.; Recker, K.; Laws, H.J.; Dirksen, U.; Troger, A.; Wieczorek, U.; Furlan, S.; Gobel, U.; Hanenberg, H. Identification of candidate target antigens for antibody-based immunotherapy in childhood B-cell precursor ALL. Klin. Padiatr. 2006, 218, 327-333.
188. Olejniczak, S.H.; Stewart, C.C.; Donohue, K.; Czuczman, M.S. A quantitative exploration of surface antigen expression in common B-cell malignancies using flow cytometry. Immunol. Invest. 2006, 35, 93-114.
189. Rawstron, A.C.; de Tute, R.; Jack, A.S.; Hillmen, P. Flow cytometric protein expression profiling as a systematic approach for developing disease-specific assays: Identification of a chronic lymphocytic leukaemia-specific assay for use in rituximab-containing regimens. Leukemia 2006, 20, 2102-2110.
190. Campana, D.; Janossy, G.; Bofill, M.; Trejdosiewicz, L.K.; Ma, D.; Hoffbrand, A.V.; Mason, D.Y.; Lebacq, A.M.; Forster, H.K. Human B cell development. I. Phenotypic differences of B lymphocytes in the bone marrow and peripheral lymphoid tissue. J. Immunol. 1985, 134, 1524-1530.
191. Mansfield, E.; Amlot, P.; Pastan, I.; FitzGerald, D.J. Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors. Blood 1997, 90, 2020-2026.
192. Robak T. Current treatment options in hairy cell leukemia and hairy cell leukemia variant. Canc. Treat. Rev. 2006, 32, 365-376.
193. Kreitman, R.J.; Pastan, I. Immunotoxins in the treatment of hematologic malignancies. Curr. Drug Targets. 2006, 7, 1301-1311.
194. Kreitman, R.J. Recombinant immunotoxins for the treatment of chemoresistant hematologic malignancies. Curr. Pharm. Des. 2009, 15, 2652-2664.
195. Sakamoto, J.; Furukawa, K.; Cordon-Cardo, C.; Yin, B.W.; Rettig, W.J.; Oettgen, H.F.; Old, L.J.; Lloyd, K.O. Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines. Canc. Res. 1986, 46, 1553-1561.
196. Miyake, M.; Taki, T.; Hitomi, S.; Hakomori, S. Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung. N. Engl. J. Med. 1992, 327, 14-18.
197. Yin, B.W.; Finstad, C.L.; Kitamura, K.; Federici, M.G.; Welshinger, M.; Kudryashov, V.; Hoskins, W.J.; Welt, S.; Lloyd, K.O. Serological and immunochemical analysis of Lewis y (Ley) blood group antigen expression in epithelial ovarian cancer. Int. J. Cancer. 1996, 65, 406-412.
198. Pastan, I.; Lovelace, E.T.; Gallo, M.G.; Rutherford, A.V.; Magnani, J.L.; Willingham, M.C. Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. Canc. Res. 1991, 51, 3781-3787.
199. Kuan, C.T.; Pai, L.H.; Pastan, I. Immunotoxins containing Pseudomonas exotoxin that target LeY damage human endothelial cells in an antibody-specific mode: Relevance to vascular leak syndrome. Clin. Canc. Res. 1995, 1, 1589-1594.
200. Posey, J.A.; Khazaeli, M.B.; Bookman, M.A.; Nowrouzi, A.; Grizzle, W.E.; Thornton, J.; Carey, D.E.; Lorenz, J.M.; Sing, A.P.; Siegall, C.B.; LoBuglio, A.F.; Saleh, M.N. A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors. Clin. Canc. Res. 2002, 8, 3092-3099.
201. Nielsen, K.; Boston, R.S. Ribosome-inactivating proteins: A plant perspective. Annu. Rev. Plant. Physiol. Plant. Mol. Biol. 2001, 52, 785-816.
202. Peumans, W.J.; Hao, Q.; Van Damme, E.J. Ribosome-inactivating proteins from plants: More than RNA N-glycosidases? FASEB J. 2001, 15, 1493-1506.
203. Van Damme, E.J.M.; Hao, Q.; Chen, Y.; Barre, A.; Vandenbussche, F.; Desmyter, S.; Rouge, P.; Peumans, W.J. Ribosome-inactivating proteins: A family of plant proteins that do more than inactivate ribosomes. Crit. Rev. Plant Sci. 2001, 20, 395-466.
204. Girbes, T.; Ferreras, J.M.; Arias, F.J.; Stirpe, F. Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria. Mini Rev. Med. Chem. 2004, 4, 461-476.
205. Hartley, M.R.; Lord, J.M. Cytotoxic ribosome-inactivating lectins from plants. Biochim. Biophys. Acta 2004, 1701, 1-14.
206. Stirpe, F. Ribosome-inactivating proteins. Toxicon 2004, 44, 371-383.
207. Stirpe, F.; Battelli, M.G. Ribosome-inactivating proteins: Progress and problems. Cell Mol. Life Sci. 2006, 63, 1850-1866.
208. Reinbothe, S.; Reinbothe, C.; Lehmann, J.; Becker, W.; Apel, K.; Parthier, B. JIP60, a methyl jasmonate-induced ribosome-inactivating protein involved in plant stress reactions. Proc. Natl. Acad. Sci. USA 1994, 91, 7012-7016.
209. Stirpe, F.; Barbieri, L.; Gorini, P.; Valbonesi, P.; Bolognesi, A.; Polito, L. Activities associated with the presence of ribosome-inactivating proteins increase in senescent and stressed leaves. FEBS Lett. 1996, 382, 309-312.
210. Rippmann, J.F.; Michalowski, C.B.; Nelson, D.E.; Bohnert, H.J. Induction of a ribosome- inactivating protein upon environmental stress. Plant. Mol. Biol. 1997, 35, 701-709.
211. Cola, A.D.; Poma, A.; Spanò, L. Culture senescence and abscisic acid induce saporin production in cultured roots of Saponaria officinalis. New Phytol. 1999, 141, 381-386.
212. Song, S.K.; Choi, Y.; Moon, Y.H.; Kim, S.G.; Choi, Y.D.; Lee, J.S. Systemic induction of a Phytolacca insularis antiviral protein gene by mechanical wounding, jasmonic acid, and abscisic acid. Plant Mol. Biol. 2000, 43, 439-450.
213. Bass, H.W.; Krawetz, J.E.; GR, O.B.; Zinselmeier, C.; Habben, J.E.; Boston, R.S. Maize ribosome-inactivating proteins (RIPs) with distinct expression patterns have similar requirements for proenzyme activation. J. Exp. Bot. 2004, 55, 2219-2233.
214. Qin, W.; Ming-Xing, H.; Ying, X.; Xin-Shen, Z.; Fang, C. Expression of a ribosome inactivating protein (curcin 2) in Jatropha curcas is induced by stress. J. Biosci. 2005, 30, 351-357.
215. Girbes, T.; de Torre, C.; Iglesias, R.; Miguel Ferreras, J.; Mendez, E. RIP for viruses. Nature 1996, 379, 777-778.
216. Iglesias, R.; Perez, Y.; de Torre, C.; Ferreras, J.M.; Antolin, P.; Jimenez, P.; Rojo, M.A.; Mendez, E.; Girbes, T. Molecular characterization and systemic induction of single-chain ribosome-inactivating proteins (RIPs) in sugar beet (Beta vulgaris) leaves. J. Exp. Bot. 2005, 56, 1675-1684.
217. Xu, J.; Wang, H.; Fan, J. Expression of a ribosome-inactivating protein gene in bitter melon is induced by Sphaerotheca fuliginea and abiotic stimuli. Biotechnol. Lett. 2007, 29, 1605-1610.
218. Walsh, T.A.; Morgan, A.E.; Hey, T.D. Characterization and molecular cloning of a proenzyme form of a ribosome-inactivating protein from maize. Novel mechanism of proenzyme activation by proteolytic removal of a 2.8-kilodalton internal peptide segment. J. Biol. Chem. 1991, 266, 23422-23427.
219. Bass, H.W.; Webster, C.; GR, O.B.; Roberts, J.K.; Boston, R.S. A maize ribosome-inactivating protein is controlled by the transcriptional activator Opaque-2. Plant Cell 1992, 4, 225-234.
220. Chaudhry, B.; Muller-Uri, F.; Cameron-Mills, V.; Gough, S.; Simpson, D.; Skriver, K.; Mundy, J. The barley 60 kDa jasmonate-induced protein (JIP60) is a novel ribosome-inactivating protein. Plant J. 1994, 6, 815-824.
221. Nicolson, G.L.; Blaustein, J. The interaction of Ricinus communis agglutinin with normal and tumor cell surfaces. Biochim. Biophys. Acta. 1972, 266, 543-547.
222. Nicolson, G.L. The interactions of lectins with animal cell surfaces. Int. Rev. Cytol. 1974, 39, 89-190.
223. Nicolson, G.L. Ultrastructural analysis of toxin binding and entry into mammalian cells. Nature 1974, 251, 628-630.
224. Baenziger, J.U.; Fiete, D. Structural determinants of Ricinus communis agglutinin and toxin specificity for oligosaccharides. J. Biol. Chem. 1979, 254, 9795-9799.
225. Houston, L.L.; Dooley, T.P. Binding of two molecules of 4-methylumbelliferyl galactose or 4-methylumbelliferyl N-acetylgalactosamine to the B chains of ricin and Ricinus communis agglutinin and to purified ricin B chain. J. Biol. Chem. 1982, 257, 4147-4151.
226. Hughes, R.C.; Mills, G. Analysis by lectin affinity chromatography of N-linked glycans of BHK cells and ricin-resistant mutants. Biochem. J. 1983, 211, 575-587.
227. Skilleter, D.N.; Paine, A.J.; Stirpe, F. A comparison of the accumulation of ricin by hepatic parenchymal and non-parenchymal cells and its inhibition of protein synthesis. Biochim. Biophys. Acta 1981, 677, 495-500.
228. Simmons, B.M.; Stahl, P.D.; Russell, J.H. Mannose receptor-mediated uptake of ricin toxin and ricin A chain by macrophages. Multiple intracellular pathways for a chain translocation. J. Biol. Chem. 1986, 261, 7912-7920.
229. Magnusson, S.; Berg, T.; Turpin, E.; Frenoy, J.P. Interactions of ricin with sinusoidal endothelial rat liver cells. Different involvement of two distinct carbohydrate-specific mechanisms in surface binding and internalization. Biochem. J. 1991, 277, 855-861.
230. Magnusson, S.; Kjeken, R.; Berg, T. Characterization of two distinct pathways of endocytosis of ricin by rat liver endothelial cells. Exp. Cell. Res. 1993, 205, 118-125.
231. Riccobono, F.; Fiani, M.L. Mannose receptor dependent uptake of ricin A1 and A2 chains by macrophages. Carbohydr. Res. 1996, 282, 285-292.
232. Frankel, A.E.; Fu, T.; Burbage, C.; Tagge, E.; Harris, B.; Vesely, J.; Willingham, M.C. Lectin- deficient ricin toxin intoxicates cells bearing the D-mannose receptor. Carbohydr. Res. 1997, 300, 251-258.
233. Rapak, A.; Falnes, P.O.; Olsnes, S. Retrograde transport of mutant ricin to the endoplasmic reticulum with subsequent translocation to cytosol. Proc. Natl. Acad. Sci. USA 1997, 94, 3783-3788.
234. Sandvig, K.; van Deurs, B. Endocytosis and intracellular transport of ricin: Recent discoveries. FEBS Lett. 1999, 452, 67-70.
235. Simpson, J.C.; Roberts, L.M.; Romisch, K.; Davey, J.; Wolf, D.H.; Lord, J.M. Ricin A chain utilises the endoplasmic reticulum-associated protein degradation pathway to enter the cytosol of yeast. FEBS Lett. 1999, 459, 80-84.
236. Wesche, J.; Rapak, A.; Olsnes, S. Dependence of ricin toxicity on translocation of the toxin A-chain from the endoplasmic reticulum to the cytosol. J. Biol. Chem. 1999, 274, 34443-34449.
237. Deeks, E.D.; Cook, J.P.; Day, P.J.; Smith, D.C.; Roberts, L.M.; Lord, J.M. The low lysine content of ricin A chain reduces the risk of proteolytic degradation after translocation from the endoplasmic reticulum to the cytosol. Biochemistry 2002, 41, 3405-3413.
238. Wesche, J. Retrograde transport of ricin. Int. J. Med. Microbiol. 2002, 291, 517-521.
239. Lord, J.M.; Deeks, E.; Marsden, C.J.; Moore, K.; Pateman, C.; Smith, D.C.; Spooner, R.A.; Watson, P.; Roberts, L.M. Retrograde transport of toxins across the endoplasmic reticulum membrane. Biochem. Soc. Trans. 2003, 31, 1260-1262.
240. Roberts, L.M.; Lord, J.M. Ribosome-inactivating proteins: Entry into mammalian cells and intracellular routing. Mini Rev. Med. Chem. 2004, 4, 505-512.
241. Spooner, R.A.; Watson, P.D.; Marsden, C.J.; Smith, D.C.; Moore, K.A.; Cook, J.P.; Lord, J.M.; Roberts, L.M. Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. Biochem. J. 2004, 383, 285-293.
242. Vago, R.; Marsden, C.J.; Lord, J.M.; Ippoliti, R.; Flavell, D.J.; Flavell, S.U.; Ceriotti, A.; Fabbrini, M.S. Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells. FEBS J. 2005, 272, 4983-4995.
243. Cavallaro, U.; Nykjaer, A.; Nielsen, M.; Soria, M.R. Alpha 2-macroglobulin receptor mediates binding and cytotoxicity of plant ribosome-inactivating proteins. Eur. J. Biochem. 1995, 232, 165-171.
244. Cavallaro, U.; Soria, M.R. Targeting plant toxins to the urokinase and alpha 2-macroglobulin receptors. Semin. Canc. Biol. 1995, 6, 269-278.
245. Chan, W.L.; Shaw, P.C.; Tam, S.C.; Jacobsen, C.; Gliemann, J.; Nielsen, M.S. Trichosanthin interacts with and enters cells via LDL receptor family members. Biochem. Biophys. Res. Commun. 2000, 270, 453-457.
246. Stirpe, F.; Olsnes, S.; Pihl, A. Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavalin A. J. Biol. Chem. 1980, 255, 6947-6953.
247. Bolognesi, A.; Tazzari, P.L.; Tassi, C.; Gromo, G.; Gobbi, M.; Stirpe, F. A comparison of anti-lymphocyte immunotoxins containing different ribosome-inactivating proteins and antibodies. Clin. Exp. Immunol. 1992, 89, 341-346.
248. Bolognesi, A.; Polito, L. Immunotoxins and other conjugates: Pre-clinical studies. Mini Rev. Med. Chem. 2004, 4, 563-583.
249. Fracasso, G.; Bellisola, G.; Castelletti, D.; Tridente, G.; Colombatti, M. Immunotoxins and other conjugates: Preparation and general characteristics. Mini Rev. Med. Chem. 2004, 4, 545-562
250. Geden, S.E.; Gardner, R.A.; Fabbrini, M.S.; Ohashi, M.; Phanstiel Iv, O.; Teter, K. Lipopolyamine treatment increases the efficacy of intoxication with saporin and an anticancer saporin conjugate. FEBS J. 2007, 274, 4825-4836.
251. Endo, Y.; Tsurugi, K. The RNA N-glycosidase activity of ricin A-chain. The characteristics of the enzymatic activity of ricin A-chain with ribosomes and with rRNA. J. Biol. Chem. 1988, 263, 8735-8739.
252. Endo, Y.; Tsurugi, K.; Lambert, J.M. The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes: The RNA N-glycosidase activity of the proteins. Biochem. Biophys. Res. Commun. 1988, 150, 1032-1036.
253. Stirpe, F.; Bailey, S.; Miller, S.P.; Bodley, J.W. Modification of ribosomal RNA by ribosome- inactivating proteins from plants. Nucl. Acid. Res. 1988, 16, 1349-1357.
254. Montanaro, L.; Sperti, S.; Mattioli, A.; Testoni, G.; Stirpe, F. Inhibition by ricin of protein synthesis in vitro. Inhibition of the binding of elongation factor 2 and of adenosine diphosphate- ribosylated elongation factor 2 to ribosomes. Biochem. J. 1975, 146, 127-131.
255. Nilsson, L.; Asano, K.; Svensson, B.; Poulsen, F.M.; Nygard, O. Reduced turnover of the elongation factor EF-1 X ribosome complex after treatment with the protein synthesis inhibitor II from barley seeds. Biochim. Biophys. Acta 1986, 868, 62-70.
256. Griffiths, G.D.; Leek, M.D.; Gee, D.J. The toxic plant proteins ricin and abrin induce apoptotic changes in mammalian lymphoid tissues and intestine. J. Pathol. 1987, 151, 221-229.
257. Brigotti, M.; Rambelli, F.; Zamboni, M.; Montanaro, L.; Sperti, S. Effect of alpha-sarcin and ribosome-inactivating proteins on the interaction of elongation factors with ribosomes. Biochem. J. 1989, 257, 723-727.
258. Osborn, R.W.; Hartley, M.R. Dual effects of the ricin A chain on protein synthesis in rabbit reticulocyte lysate. Inhibition of initiation and translocation. Eur. J. Biochem. 1990, 193, 401-407.
259. Bergamaschi, G.; Perfetti, V.; Tonon, L.; Novella, A.; Lucotti, C.; Danova, M.; Glennie, M.J.; Merlini, G.; Cazzola, M. Saporin, a ribosome-inactivating protein used to prepare immunotoxins, induces cell death via apoptosis. Br. J. Haematol. 1996, 93, 789-794.
260. Bolognesi, A.; Tazzari, P.L.; Olivieri, F.; Polito, L.; Falini, B.; Stirpe, F. Induction of apoptosis by ribosome-inactivating proteins and related immunotoxins. Int. J. Canc. 1996, 68, 349-355.
261. Bantel, H.; Engels, I.H.; Voelter, W.; Schulze-Osthoff, K.; Wesselborg, S. Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Canc. Res. 1999, 59, 2083-2090.
262. Narayanan, S.; Surolia, A.; Karande, A.A. Ribosome-inactivating protein and apoptosis: Abrin causes cell death via mitochondrial pathway in Jurkat cells. Biochem. J. 2004, 377, 233-240.
263. Mi, S.L.; An, C.C.; Wang, Y.; Chen, J.Y.; Che, N.Y.; Gao, Y.; Chen, Z.L. Trichomislin, a novel ribosome-inactivating protein, induces apoptosis that involves mitochondria and caspase-3. Arch. Biochem. Biophys. 2005, 434, 258--265.
264. Rao, P.V.; Jayaraj, R.; Bhaskar, A.S.; Kumar, O.; Bhattacharya, R.; Saxena, P.; Dash, P.K.; Vijayaraghavan, R. Mechanism of ricin-induced apoptosis in human cervical cancer cells. Biochem. Pharmacol. 2005, 69, 855-865
265. Parikh, B.A.; Tumer, N.E. Antiviral activity of ribosome inactivating proteins in medicine. Mini Rev. Med. Chem. 2004, 4, 523-543.
266. Barbieri, L.; Valbonesi, P.; Bonora, E.; Gorini, P.; Bolognesi, A.; Stirpe, F. Polynucleotide: Adenosine glycosidase activity of ribosome-inactivating proteins: Effect on DNA, RNA and poly(A). Nucl. Acid. Res. 1997, 25, 518-522.
267. Barbieri, L.; Bolognesi, A.; Valbonesi, P.; Polito, L.; Olivieri, F.; Stirpe, F. Polynucleotide: Adenosine glycosidase activity of immunotoxins containing ribosome-inactivating proteins. J. Drug Target 2000, 8, 281-288.
268. Barbieri, L.; Valbonesi, P.; Govoni, M.; Pession, A.; Stirpe, F. Polynucleotide: Adenosine glycosidase activity of saporin-L1: Effect on various forms of mammalian DNA. Biochim. Biophys. Acta 2000, 1480, 258-266.
269. Barbieri, L.; Valbonesi, P.; Righi, F.; Zuccheri, G.; Monti, F.; Gorini, P.; Samori, B.; Stirpe, F. Polynucleotide: Adenosine glycosidase is the sole activity of ribosome-inactivating proteins on DNA. J. Biochem. 2000, 128, 883-889.
270. Nicolas, E.; Beggs, J.M.; Taraschi, T.F. Gelonin is an unusual DNA glycosylase that removes adenine from single-stranded DNA, normal base pairs and mismatches. J. Biol. Chem. 2000, 275, 31399-31406.
271. Li, M.X.; Yeung, H.W.; Pan, L.P.; Chan, S.I. Trichosanthin, a potent HIV-1 inhibitor, can cleave supercoiled DNA in vitro. Nucl. Acid. Res. 1991, 19, 6309-6312.
272. Ling, J.; Li, X.; Wu, X.; Liu, W. Topological requirements for recognition and cleavage of DNA by ribosome-inactivating proteins. Biol. Chem. Hoppe. Seyler 1995, 376, 637-641.
273. Roncuzzi, L.; Gasperi-Campani, A. DNA-nuclease activity of the single-chain ribosome- inactivating proteins dianthin 30, saporin 6 and gelonin. FEBS Lett. 1996, 392, 16-20.
274. Nicolas, E.; Beggs, J.M.; Haltiwanger, B.M.; Taraschi, T.F. Direct evidence for the deoxyribonuclease activity of the plant ribosome inactivating protein gelonin. FEBS Lett. 1997, 406, 162-164.
275. Wang, P.; Tumer, N.E. Pokeweed antiviral protein cleaves double-stranded supercoiled DNA using the same active site required to depurinate rRNA. Nucl. Acid. Res. 1999, 27, 1900-1905.
276. Bagga, S.; Seth, D.; Batra, J.K. The cytotoxic activity of ribosome-inactivating protein saporin-6 is attributed to its rRNA N-glycosidase and internucleosomal DNA fragmentation activities. J. Biol. Chem. 2003, 278, 4813-4820.
277. Gasperi-Campani, A.; Brognara, I.; Baiocchi, D.; Roncuzzi, L. Mitochondrial DNA D-loop as a new target of Saporin 6 nuclease activity. Toxicon 2005, 45, 475-480.
278. Choudhary, N.L.; Yadav, O.P.; Lodha, M.L. Ribonuclease, deoxyribonuclease, and antiviral activity of Escherichia coli-expressed Bougainvillea xbuttiana antiviral protein 1. Biochemistry (Mosc) 2008, 73, 273-277.
279. Mock, J.W.; Ng, T.B.; Wong, R.N.; Yao, Q.Z.; Yeung, H.W.; Fong, W.P. Demonstration of ribonuclease activity in the plant ribosome-inactivating proteins alpha- and beta-momorcharins. Life Sci. 1996, 59, 1853-1859.
280. Fong, W.P.; Mock, W.Y.; Ng, T.B. Intrinsic ribonuclease activities in ribonuclease and ribosome-inactivating proteins from the seeds of bitter gourd. Int. J. Biochem. Cell Biol. 2000, 32, 571-577
281. Herceg, Z.; Wang, Z.Q. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat. Res. 2001, 477, 97-110.
282. Barbieri, L.; Brigotti, M.; Perocco, P.; Carnicelli, D.; Ciani, M.; Mercatali, L.; Stirpe, F. Ribosome-inactivating proteins depurinate poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase and have transforming activity for 3T3 fibroblasts. FEBS Lett. 2003, 538, 178-182.
283. Hudak, K.A.; Wang, P.; Tumer, N.E. A novel mechanism for inhibition of translation by pokeweed antiviral protein: Depurination of the capped RNA template. RNA 2000, 6, 369-380.
284. Vivanco, J.M.; Tumer, N.E. Translation Inhibition of Capped and Uncapped Viral RNAs Mediated by Ribosome-Inactivating Proteins. Phytopathology 2003, 93, 588-595.
285. Li, X.D.; Chen, W.F.; Liu, W.Y.; Wang, G.H. Large-scale preparation of two new ribosome- inactivating proteins-Cinnamomin and camphorin from the seeds of Cinnamomum camphora. Protein Expr. Purif. 1997, 10, 27-31.
286. Sharma, N.; Park, S.W.; Vepachedu, R.; Barbieri, L.; Ciani, M.; Stirpe, F.; Savary, B.J.; Vivanco, J.M. Isolation and characterization of an RIP (ribosome-inactivating protein)-like protein from tobacco with dual enzymatic activity. Plant Physiol. 2004, 134, 171-181.
287. Barbieri, L.; Polito, L.; Bolognesi, A.; Ciani, M.; Pelosi, E.; Farini, V.; Jha, A.K.; Sharma, N.; Vivanco, J.M.; Chambery, A.; Parente, A.; Stirpe, F. Ribosome-inactivating proteins in edible plants and purification and characterization of a new ribosome-inactivating protein from Cucurbita moschata. Biochim. Biophys. Acta 2006, 1760, 783-792.
288. Helmy, M.; Lombard, S.; Pieroni, G. Ricin RCA60: Evidence of its phospholipase activity. Biochem. Biophy.s Res. Commun. 1999, 258, 252-255.
289. Nicolas, E.; Goodyer, I.D.; Taraschi, T.F. An additional mechanism of ribosome-inactivating protein cytotoxicity: Degradation of extrachromosomal DNA. Biochem. J. 1997, 327, 413-417.
290. Brigotti, M.; Alfieri, R.; Sestili, P.; Bonelli, M.; Petronini, P.G.; Guidarelli, A.; Barbieri, L.; Stirpe, F.; Sperti, S. Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J. 2002, 16, 365-372.
291. Sestili, P.; Alfieri, R.; Carnicelli, D.; Martinelli, C.; Barbieri, L.; Stirpe, F.; Bonelli, M.; Petronini, P.G.; Brigotti, M. Shiga toxin 1 and ricin inhibit the repair of H2O2-induced DNA single strand breaks in cultured mammalian cells. DNA Repair (Amst) 2005, 4, 271-277.
292. Brigotti, M.; Carnicelli, D.; Ravanelli, E.; Vara, A.G.; Martinelli, C.; Alfieri, R.R.; Petronini, P.G.; Sestili, P. Molecular damage and induction of proinflammatory cytokines in human endothelial cells exposed to Shiga toxin 1, Shiga toxin 2, and alpha-sarcin. Infect. Immun. 2007, 75, 2201-2207.
293. Li, X.P.; Baricevic, M.; Saidasan, H.; Tumer, N.E. Ribosome depurination is not sufficient for ricin-mediated cell death in Saccharomyces cerevisiae. Infect. Immun. 2007, 75, 417-428.
294. Sikriwal, D.; Ghosh, P.; Batra, J.K. Ribosome inactivating protein saporin induces apoptosis through mitochondrial cascade, independent of translation inhibition. Int. J. Biochem. Cell Biol. 2008, 40, 2880-2888.
295. Polito, L.; Bortolotti, M.; Farini, V.; Battelli, M.G.; Barbieri, L.; Bolognesi, A. Saporin induces multiple death pathways in lymphoma cells with different intensity and timing as compared to ricin. Int. J. Biochem. Cell Biol. 2009, 41, 1055-1061
296. Stein, H.; Mason, D.Y.; Gerdes, J.; O'Connor, N.; Wainscoat, J.; Pallesen, G.; Gatter, K.; Falini, B.; Delsol, G.; Lemke, H.; et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: Evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985, 66, 848-858.
297. Froese, P.; Lemke, H.; Gerdes, J.; Havsteen, B.; Schwarting, R.; Hansen, H.; Stein, H. Biochemical characterization and biosynthesis of the Ki-1 antigen in Hodgkin-derived and virus- transformed human B and T lymphoid cell lines. J. Immunol. 1987, 139, 2081-2087.
298. Agnarsson, B.A.; Kadin, M.E. The immunophenotype of Reed-Sternberg cells. A study of 50 cases of Hodgkin's disease using fixed frozen tissues. Cancer 1989, 63, 2083-2087.
299. Foxwell, B.M.; Donovan, T.A.; Thorpe, P.E.; Wilson, G. The removal of carbohydrates from ricin with endoglycosidases H, F and D and alpha-mannosidase. Biochim. Biophys. Acta 1985, 840, 193-203.
300. Blakey, D.C.; Thorpe, P.E. Effect of chemical deglycosylation on the in vivo fate of ricin A-chain. Cancer Drug Deliv. 1986, 3, 189-196.
301. Bourrie, B.J.; Casellas, P.; Blythman, H.E.; Jansen, F.K. Study of the plasma clearance of antibody--ricin-A-chain immunotoxins. Evidence for specific recognition sites on the A chain that mediate rapid clearance of the immunotoxin. Eur. J. Biochem. 1986, 155, 1-10.
302. Skilleter, D.N.; Foxwell, B.M. Selective uptake of ricin A-chain by hepatic non-parenchymal cells in vitro. Importance of mannose oligosaccharides in the toxin. FEBS Lett. 1986, 196, 344-348.
303. Blakey, D.C.; Watson, G.J.; Knowles, P.P.; Thorpe, P.E. Effect of chemical deglycosylation of ricin A chain on the in vivo fate and cytotoxic activity of an immunotoxin composed of ricin A chain and anti-Thy 1.1 antibody. Canc. Res. 1987, 47, 947-952.
304. Fulton, R.J.; Tucker, T.F.; Vitetta, E.S.; Uhr, J.W. Pharmacokinetics of tumor-reactive immunotoxins in tumor-bearing mice: Effect of antibody valency and deglycosylation of the ricin A chain on clearance and tumor localization. Canc. Res. 1988, 48, 2618-2625.
305. Trown, P.W.; Reardan, D.T.; Carroll, S.F.; Stoudemire, J.B.; Kawahata, R.T. Improved pharmacokinetics and tumor localization of immunotoxins constructed with the Mr 30,000 form of ricin A chain. Canc. Res. 1991, 51, 4219-4225.
306. Mason, D.Y.; Stein, H.; Gerdes, J.; Pulford, K.A.; Ralfkiaer, E.; Falini, B.; Erber, W.N.; Micklem, K.; Gatter, K.C. Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells. Blood 1987, 69, 836-840.
307. Tedder, T.F.; Tuscano, J.; Sato, S.; Kehrl, J.H. CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Annu.Rev. Immunol. 1997, 15, 481-504.
308. Fujimoto, M.; Poe, J.C.; Inaoki, M.; Tedder, T.F. CD19 regulates B lymphocyte responses to transmembrane signals. Semin. Immunol. 1998, 10, 267-277.
309. Poe, J.C.; Hasegawa, M.; Tedder, T.F. CD19, CD21, and CD22: Multifaceted response regulators of B lymphocyte signal transduction. Int. Rev. Immunol. 2001, 20, 739-762.
310. Shen, G.L.; Li, J.L.; Ghetie, M.A.; Ghetie, V.; May, R.D.; Till, M.; Brown, A.N.; Relf, M.; Knowles, P.; Uhr, J.W.; et al. Evaluation of four CD22 antibodies as ricin A chain-containing immunotoxins for the in vivo therapy of human B-cell leukemias and lymphomas. Int. J. Canc. 1988, 42, 792-797
311. Pezzutto, A.; Dorken, B.; Rabinovitch, P.S.; Ledbetter, J.A.; Moldenhauer, G.; Clark, E.A. CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J. Immunol. 1987, 138, 2793-2799.
312. Amlot, P.L.; Stone, M.J.; Cunningham, D.; Fay, J.; Newman, J.; Collins, R.; May, R.; McCarthy, M.; Richardson, J.; Ghetie, V.; et al. A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. Blood 1993, 82, 2624-2633.
313. Fathman, C.G.; Costa, G.L.; Seroogy, C.M. Gene therapy for autoimmune disease. Clin. Immunol. 2000, 95, S39-S43.
314. Kawashiri, M.-A.; Rader, D.J. Gene therapy for lipid disorders. Curr. Control Trials Cardiovasc. Med. 2000, 1, 120-127.
315. Kouraklis, G. Gene therapy for cancer: From the laboratory to the patient. Dig. Dis. Sci. 2000, 45, 1045-1052.
316. Lyngstadaas, A. Status and potential of gene therapy in clinical medicine. Assessment of an emerging health technology through systematic survey of clinical gene therapy protocols and published results. Int. J. Technol. Assess. Health. Care 2002, 18, 645-674.
317. Wadhwa, P.D.; Zielske, S.P.; Roth, J.C.; Ballas, C.B.; Bowman, J.E.; Gerson, S.L. Cancer gene therapy: Scientific basis. Annu. Rev. Med. 2002, 53, 437-452.
318. Dishart, K.L.; Work, L.M.; Denby, L.; Baker, A.H. Gene Therapy for Cardiovascular Disease. J. Biomed. Biotechnol. 2003, 2003, 138-148.
319. Selkirk, S.M. Gene therapy in clinical medicine. Postgrad. Med. J. 2004, 80, 560-570.
320. Cathomen, T.; Weitzman, M.D. Gene repair: Pointing the finger at genetic disease. Gene Ther. 2005, 12, 1415-1416.
321. Cross, D.; Burmester, J.K. Gene therapy for cancer treatment: Past, present and future. Clin. Med. Res. 2006, 4, 218-227.
322. Chuang, Y.H.; Yang, Y.H.; Wu, S.J.; Chiang, B.L. Gene therapy for allergic diseases. Curr. Gene Ther. 2009, 9, 185-191.
323. Cao, S.; Cripps, A.; Wei, M.Q. New strategies for cancer gene therapy: Progress and opportunities. Clin. Exp. Pharm. Physiol. 2010, 37, 108-114.
324. Itaka, K.; Kataoka, K. Recent development of nonviral gene delivery systems with virus-like structures and mechanisms. Eur. J. Pharm. Biopharm. 2009, 71, 475-483.
325. Pathak, A.; Patnaik, S.; Gupta, K.C. Recent trends in non-viral vector-mediated gene delivery. Biotechnol. J. 2009, 4, 1559-1572.
326. Heilbronn, R.; Weger, S. Viral vectors for gene transfer: Current status of gene therapeutics. Handbook Exp. Pharm. 2010, 197, 143-170.
327. Moolten, F.L. Drug sensitivity (suicide) genes for selective cancer chemotherapy. Canc. Gene Ther. 1994, 1, 279-287.
328. Spencer, D.M. Developments in suicide genes for preclinical and clinical applications. Curr. Opin. Mol. Ther. 2000, 2, 433-440.
329. Ozawa, T.; Hu, J.L.; Hu, L.J.; Kong, E.L.; Bollen, A.W.; Lamborn, K.R.; Deen, D.F. Functionality of hypoxia-induced BAX expression in a human glioblastoma xenograft model. Canc. Gene Ther. 2005, 12, 449-455
330. Yang, W.S.; Park, S.O.; Yoon, A.R.; Yoo, J.Y.; Kim, M.K.; Yun, C.O.; Kim, C.W. Suicide cancer gene therapy using pore-forming toxin, streptolysin O. Mol. Canc. Ther. 2006, 5, 1610-1619.
331. Altaner, C. Prodrug cancer gene therapy. Canc. Lett 2008, 270, 191-201.
332. Maxwell, I.H.; Maxwell, F.O.; Glode, L.M. Regulated Expression of a Diphtheria Toxin A-Chain Gene Transfected into Human Cells: Possible Strategy for Inducing Cancer Cell Suicide. Canc. Res. 1986, 46, 4660-4664.
333. Walther, W.; Stein, U. Cell type specific and inducible promoters for vectors in gene therapy as an approach for cell targeting. J. Mol. Med. 1996, 74, 379-392.
334. Peng, K.W. Strategies for targeting therapeutic gene delivery. Mol. Med. Today 1999, 5, 448-453.
335. Nettelbeck, D.M.; Jerome, V.; Muller, R. Gene therapy: Designer promoters for tumour targeting. Trends Genet. 2000, 16, 174-181.
336. Haviv, Y.S.; Blackwell, J. Transcriptional regulation in cancer gene therapy. Isr. Med. Assoc. J. 2001, 3, 517-522.
337. Robson, T.; Hirst, D.G. Transcriptional Targeting in Cancer Gene Therapy. J. Biomed. Biotechnol. 2003, 2003, 110-137.
338. Dorer, D.E.; Nettelbeck, D.M. Targeting cancer by transcriptional control in cancer gene therapy and viral oncolysis. Adv.Drug. Deliv. Rev. 2009, 61, 554-571.
339. Li, Y.; McCadden, J.; Ferrer, F.; Kruszewski, M.; Carducci, M.; Simons, J.; Rodriguez, R. Prostate-specific expression of the diphtheria toxin A chain (DT-A): Studies of inducibility and specificity of expression of prostate-specific antigen promoter-driven DT-A adenoviral-mediated gene transfer. Canc. Res. 2002, 62, 2576-2582.
340. Peng, W.; Chen, J.; Huang, Y.H.; Sawicki, J.A. Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells. Gene Ther. 2005, 12, 1573-1580.
341. Peng, W.; Anderson, D.G.; Bao, Y.; Padera, R.F., Jr.; Langer, R.; Sawicki, J.A. Nanoparticulate delivery of suicide DNA to murine prostate and prostate tumors. Prostate 2007, 67, 855-862.
342. Lidor, Y.J.; Lee, W.E.; Nilson, J.H.; Maxwell, I.H.; Su, L.J.; Brand, E.; Glode, L.M. In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines. Am. J. Obstet. Gynecol. 1997, 177, 579-585.
343. Huang, Y.H.; Zugates, G.T.; Peng, W.; Holtz, D.; Dunton, C.; Green, J.J.; Hossain, N.; Chernick, M.R.; Padera, R.F., Jr.; Langer, R.; Anderson, D.G.; Sawicki, J.A. Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice. Canc. Res. 2009, 69, 6184-6191.
344. Sidi, A.A.; Ohana, P.; Benjamin, S.; Shalev, M.; Ransom, J.H.; Lamm, D.; Hochberg, A.; Leibovitch, I. Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. J. Urol. 2008, 180, 2379-2383.
345. Mizrahi, A.; Czerniak, A.; Levy, T.; Amiur, S.; Gallula, J.; Matouk, I.; Abu-lail, R.; Sorin, V.; Birman, T.; de Groot, N.; Hochberg, A.; Ohana, P. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J. Transl. Med. 2009, 7, 69.
346. Mizrahi, A.; Czerniak, A.; Ohana, P.; Amiur, S.; Gallula, J.; Matouk, I.; Abu-Lail, R.; Birman, T.; Hochberg, A.; Levy, T. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: A case report. J. Med. Case. Rep. 2010, 4, 228.
347. Abdul-Ghani, R.; Ohana, P.; Matouk, I.; Ayesh, S.; Ayesh, B.; Laster, M.; Bibi, O.; Giladi, H.; Molnar-Kimber, K.; Sughayer, M.A.; de Groot, N.; Hochberg, A. Use of Transcriptional Regulatory Sequences of Telomerase (hTER and hTERT) for Selective Killing of Cancer Cells. Mol. Ther. 2000, 2, 539-544.
348. Harrison, G.S.; Long, C.J.; Curiel, T.J.; Maxwell, F.; Maxwell, I.H. Inhibition of human immunodeficiency virus-1 production resulting from transduction with a retrovirus containing an HIV-regulated diphtheria toxin A chain gene. Hum. Gene. Ther. 1992, 3, 461-469.
349. Dinges, M.M.; Cook, D.R.; King, J.; Curiel, T.J.; Zhang, X.Q.; Harrison, G.S. HIV-regulated diphtheria toxin A chain gene confers long-term protection against HIV type 1 infection in the human promonocytic cell line U937. Hum. Gene. Ther. 1995, 6, 1437-1445.
350. Konopka, K.; Harrison, G.S.; Felgner, P.L.; Duzgunes, N. Cationic liposome-mediated expression of HIV-regulated luciferase and diphtheria toxin a genes in HeLa cells infected with or expressing HIV. Biochim. Biophys. Acta 1997, 1356, 185-197.
351. Wang, Z.; Tang, Z.; Zheng, Y.; Yu, D.; Spear, M.; Iyer, S.R.; Bishop, B.; Wu, Y. Development of a nonintegrating Rev-dependent lentiviral vector carrying diphtheria toxin A chain and human TRAF6 to target HIV reservoirs. Gene Ther. 2010, 17, 1063-1076.
352. Massuda, E.S.; Dunphy, E.J.; Redman, R.A.; Schreiber, J.J.; Nauta, L.E.; Barr, F.G.; Maxwell, I.H.; Cripe, T.P. Regulated expression of the diphtheria toxin A chain by a tumor-specific chimeric transcription factor results in selective toxicity for alveolar rhabdomyosarcoma cells. Proc. Natl. Acad. Sci. USA 1997, 94, 14701-14706.
353. Maxwell, I.H.; Kaletta, C.; Naujoks, K.; Maxwell, F. Targeting diphtheria toxin A-chain transcription to activated endothelial cells using an E-selectin promoter. Angiogenesis 2003, 6, 31-38.
354. Lee, E.J.; Jameson, J.L. Cell-specific Cre-mediated activation of the diphtheria toxin gene in pituitary tumor cells: Potential for cytotoxic gene therapy. Hum. Gene Ther. 2002, 13, 533-542.
355. Wang, C.Y.; Li, F.; Yang, Y.; Guo, H.Y.; Wu, C.X.; Wang, S. Recombinant baculovirus containing the diphtheria toxin A gene for malignant glioma therapy. Canc. Res. 2006, 66, 5798-5806.
356. Cao, G.W.; Qi, Z.T.; Pan, X.; Zhang, X.Q.; Miao, X.H.; Feng, Y.; Lu, X.H.; Kuriyama, S.; Du, P. Gene therapy for human colorectal carcinoma using human CEA promoter contro led bacterial ADP-ribosylating toxin genes human CEA: PEA & DTA gene transfer. World J. Gastroenterol. 1998, 4, 388-391.
357. Hine, C.M.; Seluanov, A.; Gorbunova, V. Use of the Rad51 promoter for targeted anti-cancer therapy. Proc.Natl. Acad. Sci. USA 2008, 105, 20810-20815.
358. Murayama, Y.; Tadakuma, T.; Kunitomi, M.; Kumai, K.; Tsutsui, K.; Yasuda, T.; Kitajima, M. Cell-specific expression of the diphtheria toxin A-chain coding sequence under the control of the upstream region of the human alpha-fetoprotein gene. J. Surg. Oncol. 1999, 70, 145-149.
359. Kunitomi, M.; Takayama, E.; Suzuki, S.; Yasuda, T.; Tsutsui, K.; Nagaike, K.; Hiroi, S.; Tadakuma, T. Selective inhibition of hepatoma cells using diphtheria toxin A under the control of the promoter/enhancer region of the human alpha-fetoprotein gene. Jpn. J. Canc. Res. 2000, 91, 343-350.
360. Maxwell, I.H.; Glode, L.M.; Maxwell, F. Expression of the diphtheria toxin A-chain coding sequence under the control of promoters and enhancers from immunoglobulin genes as a means of directing toxicity to B-lymphoid cells. Canc. Res. 1991, 51, 4299-4304.
361. Rothfels, H.; Paschen, A.; Schadendorf, D. Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanoma. Exp. Dermatol. 2003, 12, 799-810.
362. Martin, V.; Cortes, M.L.; de Felipe, P.; Farsetti, A.; Calcaterra, N.B.; Izquierdo, M. Cancer gene therapy by thyroid hormone-mediated expression of toxin genes. Canc. Res. 2000, 60, 3218-3224.
363. Showalter, S.L.; Huang, Y.H.; Witkiewicz, A.; Costantino, C.L.; Yeo, C.J.; Green, J.J.; Langer, R.; Anderson, D.G.; Sawicki, J.A.; Brody, J.R. Nanoparticulate delivery of diphtheria toxin DNA effectively kills Mesothelin expressing pancreatic cancer cells. Canc. Biol. Ther. 2008, 7, 1584-1590.
364. Fogar, P.; Navaglia, F.; Basso, D.; Zambon, C.F.; Moserle, L.; Indraccolo, S.; Stranges, A.; Greco, E.; Fadi, E.; Padoan, A.; Pantano, G.; Sanzari, M.C.; Pedrazzoli, S.; Montecucco, C.; Plebani, M. Heat-induced transcription of diphtheria toxin A or its variants, CRM176 and CRM197: Implications for pancreatic cancer gene therapy. Canc. Gene Ther. 2010, 17, 58-68.
365. Lee, J.T.; Watarai, S.; Kakidani, H.; Onuma, M.; Zhao, D.D.; Yasuda, T. Evaluation of cationic liposomes for delivery of diphtheria toxin A-chain gene to cells infected with bovine leukemia virus. J. Vet. Med. Sci. 1997, 59, 169-174.
366. Tana Watarai, S.; Lee, J.T.; Onuma, M.; Ochiai, K.; Kakidani, H.; Yasuda, T. In vivo antitumor effect of cationic liposomes containing diphtheria toxin A-chain gene on cells infected with bovine leukemia virus. J. Vet. Med. Sci. 1997, 59, 617-619.
367. Diaw, L.; Woodson, K.; Gillespie, J.W. Prostate cancer epigenetics: A review on gene regulation. Gene Regul. Syst. Bio. 2007, 1, 313-325.
368. Lilja, H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J. Clin. Invest. 1985, 76, 1899-1903.
369. Lilja, H. Structure, function, and regulation of the enzyme activity of prostate-specific antigen. World J. Urol. 1993, 11, 188-191.
370. Aumuller, G.; Seitz, J.; Lilja, H.; Abrahamsson, P.A.; von der Kammer, H.; Scheit, K.H. Species- and organ-specificity of secretory proteins derived from human prostate and seminal vesicles. Prostate 1990, 17, 31-40.
371. Wu, L.; Matherly, J.; Smallwood, A.; Adams, J.Y.; Billick, E.; Belldegrun, A.; Carey, M. Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors. Gene Ther. 2001, 8, 1416-1426.
372. Mabjeesh, N.J.; Zhong, H.; Simons, J.W. Gene therapy of prostate cancer: Current and future directions. Endocr. Relat. Canc. 2002, 9, 115-139.
373. Makarov, D.V.; Loeb, S.; Getzenberg, R.H.; Partin, A.W. Biomarkers for prostate cancer. Annu. Rev. Med. 2009, 60, 139-151.
374. Zheng, J.Y.; Chen, D.; Chan, J.; Yu, D.; Ko, E.; Pang, S. Regression of prostate cancer xenografts by a lentiviral vector specifically expressing diphtheria toxin A. Canc. Gene Ther. 2003, 10, 764-770.
375. Anderson, D.G.; Peng, W.; Akinc, A.; Hossain, N.; Kohn, A.; Padera, R.; Langer, R.; Sawicki, J.A. A polymer library approach to suicide gene therapy for cancer. Proc. Natl. Acad. Sci. USA 2004, 101, 16028-16033.
376. Picard, D. Regulation of protein function through expression of chimaeric proteins. Curr. Opin. Biotechnol. 1994, 5, 511-515.
377. Logie, C.; Stewart, A.F. Ligand-regulated site-specific recombination. Proc. Natl. Acad. Sci USA 1995, 92, 5940-5944.
378. Peng, W.; Verbitsky, A.; Bao, Y.; Sawicki, J. Regulated expression of diphtheria toxin in prostate cancer cells. Mol. Ther. 2002, 6, 537-545.
379. Cho, K.R.; Shih Ie, M. Ovarian cancer. Annu Rev Pathol 2009, 4, 287-313.
380. Tsampalas, M.; Gridelet, V.; Berndt, S.; Foidart, J.M.; Geenen, V.; Perrier d'Hauterive, S. Human chorionic gonadotropin: A hormone with immunological and angiogenic properties. J. Reprod. Immunol. 2010, 85, 93-98.
381. Eagle, K.; Ledermann, J.A. Tumor Markers in Ovarian Malignancies. The Oncologist 1997, 2, 324-329.
382. Demirtas, E.; Krishnamurthy, S.; Tulandi, T. Elevated serum beta-human chorionic gonadotropin In nonpregnant conditions. Obstet. Gynecol. Surv. 2007, 62, 675-679.
383. Scholler, N.; Fu, N.; Yang, Y.; Ye, Z.; Goodman, G.E.; Hellstrom, K.E.; Hellstrom, I. Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma. Proc. Natl. Acad. Sci. USA 1999, 96, 11531-11536.
384. Schummer, M.; Ng, W.V.; Bumgarner, R.E.; Nelson, P.S.; Schummer, B.; Bednarski, D.W.; Hassell, L.; Baldwin, R.L.; Karlan, B.Y.; Hood, L. Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 1999, 238, 375-385.
385. Wang, K.; Gan, L.; Jeffery, E.; Gayle, M.; Gown, A.M.; Skelly, M.; Nelson, P.S.; Ng, W.V.; Schummer, M.; Hood, L.; Mulligan, J. Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray. Gene 1999, 229, 101-108.
386. Hough, C.D.; Sherman-Baust, C.A.; Pizer, E.S.; Montz, F.J.; Im, D.D.; Rosenshein, N.B.; Cho, K.R.; Riggins, G.J.; Morin, P.J. Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Canc. Res. 2000, 60, 6281-6287.
387. Frierson, H.F., Jr.; Moskaluk, C.A.; Powell, S.M.; Zhang, H.; Cerilli, L.A.; Stoler, M.H.; Cathro, H.; Hampton, G.M. Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas. Hum. Pathol. 2003, 34, 605-609.
388. Ordonez, N.G. Application of mesothelin immunostaining in tumor diagnosis. Am. J. Surg. Pathol. 2003, 27, 1418-1428.
389. Li, J.; Dowdy, S.; Tipton, T.; Podratz, K.; Lu, W.G.; Xie, X.; Jiang, S.W. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev. Mol. Diagn. 2009, 9, 555-566.
390. Tanos, V.; Prus, D.; Ayesh, S.; Weinstein, D.; Tykocinski, M.L.; De-Groot, N.; Hochberg, A.; Ariel, I. Expression of the imprinted H19 oncofetal RNA in epithelial ovarian cancer. Eur. J. Obstet. Gynecol. Reprod. Biol. 1999, 85, 7-11.
391. Steenman, M.J.; Rainier, S.; Dobry, C.J.; Grundy, P.; Horon, I.L.; Feinberg, A.P. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour. Nat. Genet. 1994, 7, 433-439.
392. Ilana, A.; Orit, L.; Tamar, S.; Galina, P.; Mally, S.; Nathan, D.-G.; Abraham, H. The imprinted H19 gene as a tumor marker in bladder carcinoma. Urology 1995, 45, 335-338.
393. Kondo, M.; Suzuki, H.; Ueda, R.; Osada, H.; Takagi, K.; Takahashi, T. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 1995, 10, 1193-1198.
394. Douc-Rasy, S.; Barrois, M.; Fogel, S.; Ahomadegbe, J.C.; Stehelin, D.; Coll, J.; Riou, G. High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19. Oncogene 1996, 12, 423-430.
395. Hibi, K.; Nakamura, H.; Hirai, A.; Fujikake, Y.; Kasai, Y.; Akiyama, S.; Ito, K.; Takagi, H. Loss of H19 imprinting in esophageal cancer. Canc. Res. 1996, 56, 480-482.
396. Ariel, I.; Ayesh, S.; Perlman, E.J.; Pizov, G.; Tanos, V.; Schneider, T.; Erdmann, V.A.; Podeh, D.; Komitowski, D.; Quasem, A.S.; de Groot, N.; Hochberg, A. The product of the imprinted H19 gene is an oncofetal RNA. Mol. Pathol. 1997, 50, 34-44.
397. Ariel, I.; Miao, H.Q.; Ji, X.R.; Schneider, T.; Roll, D.; de Groot, N.; Hochberg, A.; Ayesh, S. Imprinted H19 oncofetal RNA is a candidate tumour marker for hepatocellular carcinoma. Mol. Pathol. 1998, 51, 21-25.
398. Jirtle, R.L. Genomic imprinting and cancer. Exp. Cell. Res. 1999, 248, 18-24.
399. Erdmann, V.A.; Barciszewska, M.Z.; Szymanski, M.; Hochberg, A.; Groot, N.D.; Barciszewski, J. The non-coding RNAs as riboregulators. Nucl. Acid. Res. 2001, 29, 189-193.
400. Pow-Sang, J.M.; Seigne, J.D. Contemporary management of superficial bladder cancer. Canc. Control 2000, 7, 335-339.
401. Jacobs, B.L.; Lee, C.T.; Montie, J.E. Bladder cancer in 2010: How far have we come? CA Canc. J. Clin. 2010, 60, 244-272.
402. Shay, J.W.; Zou, Y.; Hiyama, E.; Wright, W.E. Telomerase and cancer. Hum. Mol. Genet. 2001, 10, 677-685.
403. Blackburn, E.H. Switching and Signaling at the Telomere. Cell 2001, 106, 661-673.
404. Mark, J.C.; Martin, F.; Dymitr, K.; Alexander, S.; Ekkehard, S.; Ilana, A.; Mark, L.T.; Stela, M.; Joseph, I.; Nathan De, G.; Abraham, H. Developmentally Imprinted Genes as Markers for Bladder Tumor Progression. J. Urol. 1996, 155, 2120-2127.
405. Ohana, P.; Bibi, O.; Matouk, I.; Levy, C.; Birman, T.; Ariel, I.; Schneider, T.; Ayesh, S.; Giladi, H.; Laster, M.; Groot, N.D.; Hochberg, A. Use of H19 regulatory sequences for targeted gene therapy in cancer. Int. J. Canc. 2002, 98, 645-650.
406. Ohana, P.; Gofrit, O.; Ayesh, S.; Al-Sharef, W.; Mizrahi, A.; Birman, T.; Schneider, T.; Matouk, I.; Groot, N.D.; Tavdy, E.; Sidi, A.A.; Hochberg, A. Regulatory sequences of the H19 gene in DNA based therapy of bladder cancer. Gene Ther. Mol. Biol. 2004, 8, 181-192
407. Freed, E.O. HIV-1 replication. Somat. Cell. Mol. Genet. 2001, 26, 13-33.
408. Liang, C.; Wainberg, M.A. The role of Tat in HIV-1 replication: An activator and/or a suppressor? AIDS Rev. 2002, 4, 41-49.
409. Wu, Y.; Marsh, J.W. Gene transcription in HIV infection. Microb. Infect. 2003, 5, 1023-1027.
410. Pugliese, A.; Vidotto, V.; Beltramo, T.; Petrini, S.; Torre, D. A review of HIV-1 Tat protein biological effects. Cell Biochem. Funct. 2005, 23, 223-227.
411. Suhasini, M.; Reddy, T.R. Cellular proteins and HIV-1 Rev function. Curr. HIV Res. 2009, 7, 91-100.
412. Fanales-Belasio, E.; Raimondo, M.; Suligoi, B.; Butto, S. HIV virology and pathogenetic mechanisms of infection: A brief overview. Ann. Ist. Super. Sanita 2010, 46, 5-14.
413. Harrison, G.S.; Maxwell, F.; Long, C.J.; Rosen, C.A.; Glode, L.M.; Maxwell, I.H. Activation of a diphtheria toxin A gene by expression of human immunodeficiency virus-1 Tat and Rev proteins in transfected cells. Hum. Gene. Ther. 1991, 2, 53-60.
414. Harrison, G.S.; Long, C.J.; Maxwell, F.; Glode, L.M.; Maxwell, I.H. Inhibition of HIV production in cells containing an integrated, HIV-regulated diphtheria toxin A chain gene. AIDS Res. Hum. Retroviruses 1992, 8, 39-45.
415. Curiel, T.J.; Cook, D.R.; Wang, Y.; Hahn, B.H.; Ghosh, S.K.; Harrison, G.S. Long-term inhibition of clinical and laboratory human immunodeficiency virus strains in human T-cell lines containing an HIV-regulated diphtheria toxin A chain gene. Hum. Gene Ther. 1993, 4, 741-747.
416. Kedzierska, K.; Crowe, S.M. The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr. Med. Chem. 2002, 9, 1893-1903.
417. Williams, D.P.; Wen, Z.; Watson, R.S.; Boyd, J.; Strom, T.B.; Murphy, J.R. Cellular processing of the interleukin-2 fusion toxin DAB486-IL-2 and efficient delivery of diphtheria fragment A to the cytosol of target cells requires Arg194. J. Biol. Chem. 1990, 265, 20673-20677.
418. Klimpel, K.R.; Molloy, S.S.; Thomas, G.; Leppla, S.H. Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin. Proc. Natl. Acad.Sci. USA 1992, 89, 10277-10281.
419. Gordon, V.M.; Leppla, S.H. Proteolytic activation of bacterial toxins: Role of bacterial and host cell proteases. Infect. Immun. 1994, 62, 333-340.
420. Beauregard, K.E.; Collier, R.J.; Swanson, J.A. Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization. Cell. Microbiol. 2000, 2, 251-258.
421. Liu, S.; Netzel-Arnett, S.; Birkedal-Hansen, H.; Leppla, S.H. Tumor cell-selective cytotoxicity of matrix metalloproteinase-activated anthrax toxin. Canc. Res. 2000, 60, 6061-6067.
422. Liu, S.; Wang, H.; Currie, B.M.; Molinolo, A.; Leung, H.J.; Moayeri, M.; Basile, J.R.; Alfano, R.W.; Gutkind, J.S.; Frankel, A.E.; Bugge, T.H.; Leppla, S.H. Matrix metalloproteinaseactivated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J. Biol. Chem. 2008, 283, 529-540.
423. Alfano, R.W.; Leppla, S.H.; Liu, S.; Bugge, T.H.; Meininger, C.J.; Lairmore, T.C.; Mulne, A.F.; Davis, S.H.; Duesbery, N.S.; Frankel, A.E. Matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis. Mol. Canc. Res. 2009, 7, 452-461
424. Alfano, R.W.; Leppla, S.H.; Liu, S.; Bugge, T.H.; Ortiz, J.M.; Lairmore, T.C.; Duesbery, N.S.; Mitchell, I.C.; Nwariaku, F.; Frankel, A.E. Inhibition of tumor angiogenesis by the matrix metalloproteinase-activated anthrax lethal toxin in an orthotopic model of anaplastic thyroid carcinoma. Mol. Canc. Ther. 2010, 9, 190-201.
425. Liu, S.; Bugge, T.H.; Leppla, S.H. Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin. J. Biol. Chem. 2001, 276, 17976-17984.
426. Liu, S.; Aaronson, H.; Mitola, D.J.; Leppla, S.H.; Bugge, T.H. Potent antitumor activity of a urokinase-activated engineered anthrax toxin. Proc. Natl. Acad. Sci. USA 2003, 100, 657-662.
427. Abi-Habib, R.J.; Singh, R.; Liu, S.; Bugge, T.H.; Leppla, S.H.; Frankel, A.E. A urokinase- activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types. Mol. Canc. Ther. 2006, 5, 2556-2562.
428. Rono, B.; Romer, J.; Liu, S.; Bugge, T.H.; Leppla, S.H.; Kristjansen, P.E. Antitumor efficacy of a urokinase activation-dependent anthrax toxin. Mol. Canc. Ther. 2006, 5, 89-96.
429. Su, Y.; Ortiz, J.; Liu, S.; Bugge, T.H.; Singh, R.; Leppla, S.H.; Frankel, A.E. Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice. Canc. Res. 2007, 67, 3329-3336.
430. Liu, S.; Redeye, V.; Kuremsky, J.G.; Kuhnen, M.; Molinolo, A.; Bugge, T.H.; Leppla, S.H. Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin. Nat. Biotechnol. 2005, 23, 725-730.
431. Tcherniuk, S.O.; Chroboczek, J.; Balakirev, M.Y. Construction of tumor-specific toxins using ubiquitin fusion technique. Mol. Ther. 2005, 11, 196-204.
432. Abi-Habib, R.J.; Liu, S.; Bugge, T.H.; Leppla, S.H.; Frankel, A.E. A urokinase-activated recombinant diphtheria toxin targeting the granulocyte-macrophage colony-stimulating factor receptor is selectively cytotoxic to human acute myeloid leukemia blasts. Blood 2004, 104, 2143-2148.
433. Falnes, P.O.; Welker, R.; Krausslich, H.G.; Olsnes, S. Toxins that are activated by HIV type-1 protease through removal of a signal for degradation by the N-end-rule pathway. Biochem. J. 1999, 343, 199-207.
434. Law, S.K.; Wang, R.R.; Mak, A.N.; Wong, K.B.; Zheng, Y.T.; Shaw, P.C. A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells. Nucl. Acid. Res. 2010, doi: 10.1093/nar/gkq551.
435. Westermarck, J.; Kahari, V.-M. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999, 13, 781-792.
436. Stamenkovic, I. Matrix metalloproteinases in tumor invasion and metastasis. Semin. Canc. Biol. 2000, 10, 415-433.
437. Konjević, G.; Stanković, S. - Matrix metalloproteinases in the process of invasion and metastasis of breast cancer. Arch. Oncol. 2006, 14, 136-140.
438. Fingleton, B. Matrix metalloproteinases as valid clinical targets. Curr. Pharm. Des. 2007, 13, 333-346.
439. Roy, R.; Yang, J.; Moses, M.A. Matrix Metalloproteinases As Novel Biomarkers and Potential Therapeutic Targets in Human Cancer. J. Clin. Oncol. 2009, 27, 5287-5297
440. Ascenzi, P.; Visca, P.; Ippolito, G.; Spallarossa, A.; Bolognesi, M.; Montecucco, C. Anthrax toxin: A tripartite lethal combination. FEBS Lett. 2002, 531, 384-388.
441. Collier, R.J.; Young, J.A. Anthrax toxin. Annu. Rev. Cell Dev. Biol. 2003, 19, 45-70.
442. Young, J.A.; Collier, R.J. Anthrax toxin: Receptor binding, internalization, pore formation, and translocation. Annu. Rev. Biochem. 2007, 76, 243-265.
443. Bradley, K.A.; Mogridge, J.; Mourez, M.; Collier, R.J.; Young, J.A. Identification of the cellular receptor for anthrax toxin. Nature 2001, 414, 225-229.
444. Scobie, H.M.; Rainey, G.J.; Bradley, K.A.; Young, J.A. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc. Natl. Acad. Sci. USA 2003, 100, 5170-5174.
445. Milne, J.C.; Furlong, D.; Hanna, P.C.; Wall, J.S.; Collier, R.J. Anthrax protective antigen forms oligomers during intoxication of mammalian cells. J. Biol. Chem. 1994, 269, 20607-20612.
446. Abrami, L.; Liu, S.; Cosson, P.; Leppla, S.H.; van der Goot, F.G. Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J. Cell. Biol. 2003, 160, 321-328.
447. Abrami, L.; Bischofberger, M.; Kunz, B.; Groux, R.; Van der Goot, F. Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors. PLoS Pathog. 2010, 6, e1000792.
448. Abrami, L.; Lindsay, M.; Parton, R.G.; Leppla, S.H.; van der Goot, F.G. Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway. J. Cell. Biol. 2004, 166, 645-651.
449. Blaustein, R.O.; Koehler, T.M.; Collier, R.J.; Finkelstein, A. Anthrax toxin: Channel-forming activity of protective antigen in planar phospholipid bilayers. Proc. Natl. Acad. Sci. USA 1989, 86, 2209-2213.
450. Milne, J.C.; Collier, R.J. pH-dependent permeabilization of the plasma membrane of mammalian cells by anthrax protective antigen. Mol. Microbiol. 1993, 10, 647-653.
451. Finkelstein, A. The channel formed in planar lipid bilayers by the protective antigen component of anthrax toxin. Toxicology 1994, 87, 29-41.
452. Krantz, B.A.; Melnyk, R.A.; Zhang, S.; Juris, S.J.; Lacy, D.B.; Wu, Z.; Finkelstein, A.; Collier, R.J. A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore. Science 2005, 309, 777-781.
453. Krantz, B.A.; Finkelstein, A.; Collier, R.J. Protein Translocation through the Anthrax Toxin Transmembrane Pore is Driven by a Proton Gradient. J. Mol. Biol. 2006, 355, 968-979.
454. Tamayo, A.G.; Bharti, A.; Trujillo, C.; Harrison, R.; Murphy, J.R. COPI coatomer complex proteins facilitate the translocation of anthrax lethal factor across vesicular membranes in vitro. Proc. Natl. Acad.Sci. USA 2008, 105, 5254-5259.
455. Collier, R.J. Membrane translocation by anthrax toxin. Mol. Aspects Med. 2009, 30, 413-422.
456. Finkelstein, A. Proton-coupled protein transport through the anthrax toxin channel. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2009, 364, 209-215.
457. Van der Goot, G.; Young, J.A. Receptors of anthrax toxin and cell entry. Mol. Aspects Med. 2009, 30, 406-412
458. Duesbery, N.S.; Webb, C.P.; Leppla, S.H.; Gordon, V.M.; Klimpel, K.R.; Copeland, T.D.; Ahn, N.G.; Oskarsson, M.K.; Fukasawa, K.; Paull, K.D.; Vande Woude, G.F. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 1998, 280, 734-737.
459. Duesbery, N.S.; Vande Woude, G.F. Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. J. Appl. Microbiol. 1999, 87, 289-293.
460. Pellizzari, R.; Guidi-Rontani, C.; Vitale, G.; Mock, M.; Montecucco, C. Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha. FEBS Lett. 1999, 462, 199-204.
461. Vitale, G.; Pellizzari, R.; Recchi, C.; Napolitani, G.; Mock, M.; Montecucco, C. Anthrax lethal factor cleaves the N-terminus of MAPKKS and induces tyrosine/threonine phosphorylation of MAPKS in cultured macrophages. J. Appl. Microbiol. 1999, 87, 288.
462. Vitale, G.; Bernardi, L.; Napolitani, G.; Mock, M.; Montecucco, C. Susceptibility of mitogen- activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem. J. 2000, 352, 739-745.
463. Park, J.M.; Greten, F.R.; Li, Z.W.; Karin, M. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 2002, 297, 2048-2051.
464. Agrawal, A.; Lingappa, J.; Leppla, S.H.; Agrawal, S.; Jabbar, A.; Quinn, C.; Pulendran, B. Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 2003, 424, 329-334.
465. Chopra, A.P.; Boone, S.A.; Liang, X.; Duesbery, N.S. Anthrax lethal factor proteolysis and inactivation of MAPK kinase. J. Biol. Chem. 2003, 278, 9402-9406.
466. Tonello, F.; Montecucco, C. The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity. Mol. Aspects Med. 2009, 30, 431-438.
467. Leppla, S.H. Anthrax toxin edema factor: A bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc. Natl. Acad. Sci. USA 1982, 79, 3162-3166.
468. Leppla, S.H. Bacillus anthracis calmodulin-dependent adenylate cyclase: Chemical and enzymatic properties and interactions with eucaryotic cells. Adv. Cyclic Nucl. Protein Phosph. Res. 1984, 17, 189-198.
469. Drum, C.L.; Yan, S.Z.; Sarac, R.; Mabuchi, Y.; Beckingham, K.; Bohm, A.; Grabarek, Z.; Tang, W.J. An extended conformation of calmodulin induces interactions between the structural domains of adenylyl cyclase from Bacillus anthracis to promote catalysis. J. Biol. Chem. 2000, 275, 36334-36340.
470. Drum, C.L.; Yan, S.Z.; Bard, J.; Shen, Y.Q.; Lu, D.; Soelaiman, S.; Grabarek, Z.; Bohm, A.; Tang, W.J. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature 2002, 415, 396-402.
471. Ulmer, T.S.; Soelaiman, S.; Li, S.; Klee, C.B.; Tang, W.J.; Bax, A. Calcium dependence of the interaction between calmodulin and anthrax edema factor. J. Biol. Chem. 2003, 278, 29261-29266.
472. Shen, Y.; Zhukovskaya, N.L.; Guo, Q.; Florian, J.; Tang, W.J. Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor. EMBO J. 2005, 24, 929-941
473. Di Nezza, L.A.; Misajon, A.; Zhang, J.; Jobling, T.; Quinn, M.A.; Ostor, A.G.; Nie, G.; Lopata, A.; Salamonsen, L.A. Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion. Cancer 2002, 94, 1466-1475.
474. Sato, T.; Sakai, T.; Noguchi, Y.; Takita, M.; Hirakawa, S.; Ito, A. Tumor-stromal cell contact promotes invasion of human uterine cervical carcinoma cells by augmenting the expression and activation of stromal matrix metalloproteinases. Gynecol. Oncol. 2004, 92, 47-56.
475. Berube, M.; Deschambeault, A.; Boucher, M.; Germain, L.; Petitclerc, E.; Guerin, S.L. MMP-2 expression in uveal melanoma: Differential activation status dictated by the cellular environment. Mol. Vis. 2005, 11, 1101-1111.
476. Roomi, M.W.; Monterrey, J.C.; Kalinovsky, T.; Rath, M.; Niedzwiecki, A. Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncol. Rep. 2009, 21, 1323-1333.
477. Arora, N.; Klimpel, K.R.; Singh, Y.; Leppla, S.H. Fusions of anthrax toxin lethal factor to the ADP-ribosylation domain of Pseudomonas exotoxin A are potent cytotoxins which are translocated to the cytosol of mammalian cells. J. Biol. Chem. 1992, 267, 15542-15548.
478. Arora, N.; Leppla, S.H. Residues 1-254 of anthrax toxin lethal factor are sufficient to cause cellular uptake of fused polypeptides. J. Biol. Chem. 1993, 268, 3334-3341.
479. Milne, J.C.; Blanke, S.R.; Hanna, P.C.; Collier, R.J. Protective antigen-binding domain of anthrax lethal factor mediates translocation of a heterologous protein fused to its amino- or carboxy-terminus. Mol. Microbiol. 1995, 15, 661-666.
480. Davies, H.; Bignell, G.R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M.J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.; Hall, S.; Hawes, R.; Hughes, J.; Kosmidou, V.; Menzies, A.; Mould, C.; Parker, A.; Stevens, C.; Watt, S.; Hooper, S.; Wilson, R.; Jayatilake, H.; Gusterson, B.A.; Cooper, C.; Shipley, J.; Hargrave, D.; Pritchard-Jones, K.; Maitland, N.; Chenevix-Trench, G.; Riggins, G.J.; Bigner, D.D.; Palmieri, G.; Cossu, A.; Flanagan, A.; Nicholson, A.; Ho, J.W.C.; Leung, S.Y.; Yuen, S.T.; Weber, B.L.; Seigler, H.F.; Darrow, T.L.; Paterson, H.; Marais, R.; Marshall, C.J.; Wooster, R.; Stratton, M.R.; Futreal, P.A. Mutations of the BRAF gene in human cancer. Nature 2002, 417, 949-954.
481. Koo, H.M.; VanBrocklin, M.; McWilliams, M.J.; Leppla, S.H.; Duesbery, N.S.; Woude, G.F. Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase. Proc. Natl. Acad. Sci. USA 2002, 99, 3052-3057.
482. Sebolt-Leopold, J.S.; Herrera, R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat. Rev. Canc. 2004, 4, 937-947.
483. Abi-Habib, R.J.; Urieto, J.O.; Liu, S.; Leppla, S.H.; Duesbery, N.S.; Frankel, A.E. BRAF status and mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 activity indicate sensitivity of melanoma cells to anthrax lethal toxin. Mol. Canc. Ther. 2005, 4, 1303-1310.
484. Abi-Habib, R.J.; Singh, R.; Leppla, S.H.; Greene, J.J.; Ding, Y.; Berghuis, B.; Duesbery, N.S.; Frankel, A.E. Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. Clin. Canc. Res. 2006, 12, 7437-7443.
485. Moayeri, M.; Haines, D.; Young, H.A.; Leppla, S.H. Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. J. Clin. Invest. 2003, 112, 670-682.
486. Turpeenniemi-Hujanen, T. Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie 2010, 87, 287-297.
487. Kurizaki, T.; Toi, M.; Tominaga, T. Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. Oncol. Rep. 1998, 5, 673-677.
488. Rundhaug, J.E. Matrix Metalloproteinases, Angiogenesis, and Cancer. Clin. Canc. Res. 2003, 9, 551-554.
489. Rundhaug, J.E. Matrix metalloproteinases and angiogenesis. J. Cell. Mol. Med. 2005, 9, 267-285.
490. Alfano, R.W.; Leppla, S.H.; Liu, S.; Bugge, T.H.; Duesbery, N.S.; Frankel, A.E. Potent inhibition of tumor angiogenesis by the matrix metalloproteinase-activated anthrax lethal toxin: Implications for broad anti-tumor efficacy. Cell Cycle 2008, 7, 745-749.
491. Syrovets, T.; Simmet, T. Novel aspects and new roles for the serine protease plasmin. Cell. Mol. Life Sci. 2004, 61, 873-885.
492. Petersen, L.C. Kinetics of reciprocal pro-urokinase/plasminogen activation-Stimulation by a template formed by the urokinase receptor bound to poly(D-lysine). Eur. J. Biochem. 1997, 245, 316-323.
493. Duffy, M.J.; Duggan, C. The urokinase plasminogen activator system: A rich source of tumour markers for the individualised management of patients with cancer. Clin. Biochem. 2004, 37, 541-548.
494. Kilpatrick, L.M.; Harris, R.L.; Owen, K.A.; Bass, R.; Ghorayeb, C.; Bar-Or, A.; Ellis, V. Initiation of plasminogen activation on the surface of monocytes expressing the type II transmembrane serine protease matriptase. Blood 2006, 108, 2616-2623.
495. Moran, P.; Li, W.; Fan, B.; Vij, R.; Eigenbrot, C.; Kirchhofer, D. Pro-urokinase-type plasminogen activator is a substrate for hepsin. J. Biol. Chem. 2006, 281, 30439-30446.
496. McMahon, B.; Kwaan, H.C. The plasminogen activator system and cancer. Pathophysiol. Haemost. Thromb. 2008, 36, 184-194.
497. Andronicos, N.M.; Chen, E.I.; Baik, N.; Bai, H.; Parmer, C.M.; Kiosses, W.B.; Kamps, M.P.; Yates, J.R.; III; Parmer, R.J.; Miles, L.A. Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-RKT, a major regulator of cell surface plasminogen activation. Blood 2010, 115, 1319-1330.
498. Strickland, D.K. A new plasminogen receptor. Blood 2010, 115, 1315-1316.
499. Andreasen, P.A.; Egelund, R.; Petersen, H.H. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell. Mol. Life. Sci. 2000, 57, 25-40.
500. Dass, K.; Ahmad, A.; Azmi, A.S.; Sarkar, S.H.; Sarkar, F.H. Evolving role of uPA/uPAR system in human cancers. Canc. Treat. Rev. 2008, 34, 122-136.
501. Cunningham, K.; Lacy, D.B.; Mogridge, J.; Collier, R.J. Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen. Proc. Nat.l Acad. Sci. USA 2002, 99, 7049-7053.
502. Mogridge, J.; Cunningham, K.; Lacy, D.B.; Mourez, M.; Collier, R.J. The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen. Proc. Natl. Acad. Sci. USA 2002, 99, 7045-7048.
503. Patick, A.K.; Potts, K.E. Protease inhibitors as antiviral agents. Clin. Microbiol. Rev. 1998, 11, 614-627.
504. Tong, L. Viral proteases. Chem. Rev. 2002, 102, 4609-4626.
505. Hsu, J.T.; Wang, H.C.; Chen, G.W.; Shih, S.R. Antiviral drug discovery targeting to viral proteases. Curr. pharm. Des. 2006, 12, 1301-1314.
506. Varshavsky, A. The N-end rule. Cold Spring Harb. Symp. Quant. Biol. 1995, 60, 461-478.
507. Varshavsky, A. The N-end rule: Functions, mysteries, uses. Proc. Natl. Acad. Sci. USA 1996, 93, 12142-12149.
508. Varshavsky, A. The N-end rule pathway of protein degradation. Genes Cells 1997, 2, 13-28.
509. Varshavsky, A. The N-end rule and regulation of apoptosis. Nat. Cell Biol. 2003, 5, 373-376.
510. Mogk, A.; Schmidt, R.; Bukau, B. The N-end rule pathway for regulated proteolysis: Prokaryotic and eukaryotic strategies. Trends Cell Biol. 2007, 17, 165-172.
511. Ravid, T.; Hochstrasser, M. Diversity of degradation signals in the ubiquitin-proteasome system. Nat. Rev. Mol. Cell. Biol. 2008, 9, 679-689.
512. Falnes, P.O.; Olsnes, S. Modulation of the intracellular stability and toxicity of diphtheria toxin through degradation by the N-end rule pathway. EMBO J. 1998, 17, 615-625.
513. Wesche, J.; Elliott, J.L.; Falnes, P.O.; Olsnes, S.; Collier, R.J. Characterization of Membrane Translocation by Anthrax Protective Antigen. Biochemistry 1998, 37, 15737-15746.
514. Kaplan, A.H.; Swanstrom, R. Human immunodeficiency virus type 1 Gag proteins are processed in two cellular compartments. Proc. Natl.Acad. Sci. USA 1991, 88, 4528-4532.
515. Riviere, Y.; Blank, V.; Kourilsky, P.; Israel, A. Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. Nature 1991, 350, 625-626.
516. Adams, L.D.; Tomasselli, A.G.; Robbins, P.; Moss, B.; Heinrikson, R.L. HIV-1 protease cleaves actin during acute infection of human T-lymphocytes. AIDS Res. Hum. Retroviruses 1992, 8, 291-295.
517. Konvalinka, J.; Litterst, M.A.; Welker, R.; Kottler, H.; Rippmann, F.; Heuser, A.M.; Krausslich, H.G. An active-site mutation in the human immunodeficiency virus type 1 proteinase (PR) causes reduced PR activity and loss of PR-mediated cytotoxicity without apparent effect on virus maturation and infectivity. J. Virol. 1995, 69, 7180-7186.
518. Nie, Z.; Bren, G.D.; Vlahakis, S.R.; Schimnich, A.A.; Brenchley, J.M.; Trushin, S.A.; Warren, S.; Schnepple, D.J.; Kovacs, C.M.; Loutfy, M.R.; Douek, D.C.; Badley, A.D. Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo. J. Virol. 2007, 81, 6947-6956.
519. Gump, J.M.; Dowdy, S.F. TAT transduction: The molecular mechanism and therapeutic prospects. Trends Mol. Med. 2007, 13, 443-448.
520. Frankel, A.E.; Tagge, E.P.; Willingham, M.C. Clinical trials of targeted toxins. Semin. Canc. Biol. 1995, 6, 307-317.
521. Baluna, R.; Vitetta, E.S. Vascular leak syndrome: A side effect of immunotherapy. Immunopharmacology 1997, 37, 117-132.
522. Baluna, R.; Rizo, J.; Gordon, B.E.; Ghetie, V.; Vitetta, E.S. Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome. Proc. Natl. Acad. Sci. USA 1999, 96, 3957-3962.
523. Kreitman, R.J. Taming ricin toxin. Nat. Biotech. 2003, 21, 372-374.
524. Smallshaw, J.E.; Ghetie, V.; Rizo, J.; Fulmer, J.R.; Trahan, L.L.; Ghetie, M.-A.; Vitetta, E.S. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat. Biotech. 2003, 21, 387-391.
525. Zhang, Q.; Chen, G.; Liu, X.; Qian, Q. Monoclonal antibodies as therapeutic agents in oncology and antibody gene therapy. Cell Res. 2007, 17, 89-99.
526. da Silva, F.A.; Corte-Real, S.; Goncalves, J., Recombinant Antibodies as Therapeutic Agents: Pathways for Modeling New Biodrugs. BioDrugs 2008, 22, 301-314.
527. Tsutsumi, Y.; Onda, M.; Nagata, S.; Lee, B.; Kreitman, R.J.; Pastan, I. Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity. Proc. Natl. Acad. Sci. USA 2000, 97, 8548-8553.
528. Hu, R.-G.; Zhai, Q.-W.; He, W.-J.; Mei, L.; Liu, W.-Y. Bioactivities of ricin retained and its immunoreactivity to anti-ricin polyclonal antibodies alleviated through pegylation. Int. J. Biochem. Cell Biol. 2002, 34, 396-402.
529. Filpula, D.; Yang, K.; Basu, A.; Hassan, R.; Xiang, L.; Zhang, Z.; Wang, M.; Wang, Q.-c.; Ho, M.; Beers, R.; Zhao, H.; Peng, P.; Zhou, J.; Li, X.; Petti, G.; Janjua, A.; Liu, J.; Wu, D.; Yu, D.; Zhang, Z.; Longley, C.; FitzGerald, D.; Kreitman, R.J.; Pastan, I. Releasable PEGylation of Mesothelin Targeted Immunotoxin SS1P Achieves Single Dosage Complete Regression of a Human Carcinoma in Mice. Bioconjug. Chem. 2007, 18, 773-784.
530. Pai, L.H.; FitzGerald, D.J.; Tepper, M.; Schacter, B.; Spitalny, G.; Pastan, I. Inhibition of Antibody Response to Pseudomonas Exotoxin and an Immunotoxin Containing Pseudomonas Exotoxin by 15-Deoxyspergualin in Mice. Canc. Res. 1990, 50, 7750-7753.
531. Siegall, C.B.; Haggerty, H.G.; Warner, G.L.; Chace, D.; Mixan, B.; Linsley, P.S.; Davidson, T. Prevention of immunotoxin-induced immunogenicity by coadministration with CTLA4Ig enhances antitumor efficacy. J. Immunol. 1997, 159, 5168-5173.
532. Gelber, E.E.; Vitetta, E.S. Effect of immunosuppressive agents on the immunogenicity and efficacy of an immunotoxin in mice. Clin. Canc. Res. 1998, 4, 1297-1304.
533. Onda, M.; Nagata, S.; FitzGerald, D.J.; Beers, R.; Fisher, R.J.; Vincent, J.J.; Lee, B.; Nakamura, M.; Hwang, J.; Kreitman, R.J.; Hassan, R.; Pastan, I. Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. J. Immunol. 2006, 177, 8822-8834.
534. Onda, M.; Beers, R.; Xiang, L.; Nagata, S.; Wang, Q.C.; Pastan, I. An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proc. Natl. Acad. Sci. USA 2008, 105, 11311-11316.
535. Stish, B.J.; Oh, S.; Chen, H.; Dudek, A.Z.; Kratzke, R.A.; Vallera, D.A. Design and modification of EGF4KDEL 7Mut, a novel bispecific ligand-directed toxin, with decreased immunogenicity and potent anti-mesothelioma activity. Br. J. Canc. 2009, 101, 1114-1123.