Immunotoxins in cancer therapy

Current Opinion in Immunology

Volumn 11, Issue 5, 1999, Pages 570-578

  Kreitman, Robert J ^a  

^a Laboratory of Biochemistry   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOTOXIN; MEMBRANE ANTIGEN; TUMOR ANTIGEN;

CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER SURGERY; CATALYSIS; CELL KILLING; CYTOSOL; DRUG EFFICACY; HEMATOLOGIC DISEASE; HUMAN; IMMUNOGENICITY; INTERNALIZATION; NONHUMAN; PROTEIN SYNTHESIS INHIBITION; REVIEW; SOLID TUMOR; TARGET CELL; TOXICITY;

EID: 0032879545     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(99)00005-9     Document Type: Review

References (97)

1. Landis SH, Murray T, Bolden S, Wingo PA Cancer statistics, 1998. CA Cancer J Clin. 48:1998;6-29.
2. Ghetie V, Till MA, Ghetie MA, Uhr JW, Vitetta ES Large scale preparation of an immunoconjugate constructed with human recombinant CD4 and deglycosylated ricin A chain. J Immunol Methods. 126:1990;135-141.
3. Pai LH, Wittes R, Setser A, Willingham MC, Pastan I Treatment of advanced solid tumors with immunotoxin LMB-1: an antibody linked to Pseudomonas exotoxin. Nat Med. 2:1996;350-353.
4. Ghetie V, Swindell E, Uhr JW, Vitetta ES Purification and properties of immunotoxins containing one vs. two deglycosylated ricin A chains. J Immunol Methods. 166:1993;117-122.
5. Studier FW, Moffatt BA Use of bacteriophage T7 polymerase to direct selective expression of cloned genes. J Mol Biol. 189:1986;113-130.
6. Buchner J, Pastan I, Brinkmann U A method for increasing the yield of properly folded recombinant fusion proteins: single-chain immunotoxins from renaturation of bacterial inclusion bodies. Anal Biochem. 205:1992;263-270.
7. 4E, a recombinant fusion of interleukin 6 with Pseudomonas exotoxin. Bioconjug Chem. 4:1993;581-585.
8. Kreitman RJ, Pastan I Using cytokine receptors to target leukemia and lymphoma with fusion toxins. Methods in Molecular Medicine: Drug Targeting. 1999;. in press.
9. Kreitman RJ, 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. 90:1997;252-259.
10. 389IL2 (Figure 1). Major responses were seen in 13 out of 35 patients with CTCL and 3 out of 17 patients with non-Hodgkin's lymphoma. The maximum tolerated dose was 27 μg/kg/day x5 due to asthenia. Most of the CTCL patients showed significant improvement in skin lesions.
11. Williams MD, Rostovtsev A, Narla RK, Uckun FM Production of recombinant DT(ct)GMCSF fusion toxin in a baculovirus expression vector system for biotherapy of GMCSF-receptor positive hematologic malignancies. Protein Expr Purif. 13:1998;210-221.
12. Kreitman RJ, Bailon P, Chaudhary VK, FitzGerald DJP, 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. 83:1994;426-434.
13. Malmqvist M BIACORE: an affinity biosensor system for characterization of biomolecular interactions. Biochem Soc Trans. 27:1999;335-340.
14. Kiyokawa T, Shirono K, Hattori T, Nishimura H, Yamaguchi K, Nichols JC, Strom TB, Murphy JR, Takatsuki K Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia. Cancer Res. 49:1989;4042-4046.
15. Kreitman RJ, Chaudhary VK, Kozak RW, FitzGerald DJP, Waldmann TA, Pastan I Recombinant toxins containing the variable domains of the anti-Tac monoclonal antibody to the interleukin-2 receptor kill malignant cells from patients with chronic lymphocytic leukemia. Blood. 80:1992;2344-2352.
16. Kreitman RJ, Chaudhary VK, Waldmann T, Willingham MC, FitzGerald DJ, Pastan I The recombinant immunotoxin anti-Tac(Fv)-Pseuodomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukemia. Proc Natl Acad Sci USA. 87:1990;8291-8295.
17. Engert A, Martin G, Amlot P, Wijdenes J, Diehl V, Thorpe P Immunotoxins constructed with anti-CD25 monoclonal antibodies and deglycosylated ricin A-chain have potent anti-tumour effects against human Hodgkin cells in vitro and solid Hodgkin tumours in mice. Int J Cancer. 49:1991;450-456.
18. Ghetie M-A, Richardson J, Tucker T, Jones D, Uhr JW, Vitetta ES Antitumor activity of Fab' and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites. Cancer Res. 51:1991;5876-5880.
19. Skrepnik N, Zieske AW, Robert E, Bravo JC, Mera R, Hunt JD Aggressive administration of recombinant oncotoxin AR209 (anti-ErbB-2) in athymic nude mice implanted with orthotopic human non-small cell lung tumours. Eur J Cancer. 34:1998;1628-1633.
20. Waurzyniak B, Schneider EA, Tumer N, Yanishevski Y, Gunther R, Chelstrom LM, Wendorf H, Myers DE, Irvin JD, Messinger Yet al. In vivo toxicity, pharmacokinetics, and antileukemic activity of TXU (anti-CD7)-pokeweed antiviral protein immunotoxin. Clin Cancer Res. 3:1997;881-890.
21. Puri RK, Hoon DS, Leland P, Snoy P, Rand RW, Pastan I, Kreitman RJ Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res. 56:1996;5631-5637.
22. Amlot PL, Stone MJ, Cunningham D, Fay J, Newman J, Collins R, May R, McCarthy M, Richardson J, Ghetie Vet 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. 82:1993;2624-2633.
23. Sausville EA, Headlee D, Stetler-Stevenson M, Jaffe ES, Solomon D, Figg WD, Herdt J, Kopp WC, Rager H, Steinberg SMet al. Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. Blood. 85:1995;3457-3465.
24. Senderowicz AM, Vitetta E, Headlee D, Ghetie V, Uhr JW, Figg WD, Lush RM, Stetler-Stevenson M, Kershaw G, Kingma DWet al. Complete sustained response of a refractory, post-transplantation, large B-cell lymphoma to an anti-CD22 immunotoxin. Ann Intern Med. 126:1997;882-885.
25. Scheuermann RH, Racila E CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 18:1995;385-397.
26. Stone MJ, Sausville EA, Fay JW, Headlee D, Collins RH, Figg WD, Stetler-Stevenson M, Jain V, Jaffe ES, Solomon Det al. A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma. Blood. 88:1996;1188-1197.
27. Conry RM, Khazaeli MB, Saleh MN, Ghetie V, Vitetta ES, Liu TP, LoBuglio AF 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. 18:1995;231-241.
28. Grossbard ML, Freedman AS, Ritz J, Coral F, Goldmacher VS, Eliseo L, Spector N, Dear K, Lambert JM, Blattler WAet al. Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion. Blood. 79:1992;576-585.
29. Grossbard ML, Lambert JM, Goldmacher VS, Spector NL, Kinsella J, Eliseo L, Coral F, Taylor JA, Blattler WA, Epstein CL, Nadler LM Anti-B4-blocked ricin: a Phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J Clin Oncol. 11:1993;726-737.
30. Multani PS, O'Day S, Nadler LM, Grossbard ML Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma. Clin Cancer Res. 4:1998;2599-2604. Multani et al. show that the chemical conjugate composed of the anti-CD19 MAb anti-B4 and 'blocked' whole ricin reaches tumor cells in the marrow more easily than tumor cells in lymph nodes, indicating that tumor penetration is a limiting factor in obtaining responses.
31. Scadden DT, Schenkein DP, Bernstein Z, Luskey B, Doweiko J, Tulpule A, Levine AM Immunotoxin combined with chemotherapy for patients with AIDS-related non-Hodgkin's lymphoma. Cancer. 83:1998;2580-2587.
32. Kreitman RJ, Wang QC, FitzGerald DJP, Pastan I Complete regression of human B-cell lymphoma xenografts in mice treated with recombinant anti-CD22 immunotoxin RFB4(dsFv)-PE38 at doses tolerated by Cynomolgus monkeys. Int J Cancer. 81:1999;148-155.
33. Y damage human endothelial cells in an antibody-specific mode: relevance to vascular leak syndrome. Clin Cancer Res. 1:1995;1589-1594.
34. Soler-Rodriguez A-M, Ghetie M-A, Oppenheimer-Marks N, Uhr JW, Vitetta ES Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: implications for vascular leak syndrome. Exp Cell Res. 206:1993;227-234.
35. Re GG, Waters C, Poisson L, Willingham MC, Sugamura K, Frankel AE Interleukin 2 (IL-2) receptor expression and sensitivity to diphtheria fusion toxin DAB(389)IL-2 in cultured hematopoietic cells. Cancer Res. 56:1996;2590-2595.
36. Waters CA, Schimke PA, Snider CE, Itoh K, Smith KA, Nichols JC, Strom TB, Murphy JR Interleukin 2 receptor-targeted cytotoxicity. Receptor binding requirements for entry of a diphtheria toxin-related interleukin 2 fusion protein into cells. Eur J Immunol. 20:1990;785-791.
37. Duvic M, Kuzel T, Olsen E, Martin A, Foss F, Kim Y, Heald P, Bacha P, Nichols J, Cabanillas F Quality of life is significantly improved in CTCL patients who responded to DAB389IL-2 (ONTAK) fusion protein. Blood. 92(suppl 1):1998;2572.
38. 486-IL-2). Fragment B sequences required for the delivery of fragment A to the cytosol of target cells. J Biol Chem. 265:1990;11885-11889.
39. 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. 60:1990;181-186.
40. Kodaka T, Uchiyama T, Ishikawa T, Kamio M, Onishi R, Itoh K, Hori T, Uchino H, Tsudo M, Araki K Interleukin-2 receptor β-chain (p70-75) expressed on leukemic cells from adult T cell leukemia patients. Jpn J Cancer Res. 81:1990;902-908.
41. Kreitman RJ, Pastan I Targeting Pseudomonas exotoxin to hematologic malignancies. Semin Cancer Biol. 6:1995;297-306.
42. Mavroudis DA, Jiang YZ, Hensel N, Lewalle P, Couriel D, Kreitman RJ, Pastan I, Barrett AJ Specific depletion of alloreactivity against haplotype mismatched related individuals: a new approach to graft-versus-host disease prophylaxis in haploidentical bone marrow transplantation. Bone Marrow Transplant. 17:1996;793-799.
43. Engert A, Diehl V, Schnell R, Radszuhn A, Hatwig MT, Drillich S, Schon G, Bohlen H, Tesch H, Hansmann MLet al. A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. Blood. 89:1997;403-410.
44. Schnell R, Vitetta E, Schindler J, Barth S, Winkler U, Borchmann P, Hansmann ML, 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. 30:1998;525-537.
45. Montagna D, Yvon E, Calcaterra V, Comoli P, Locatelli F, Maccario R, Fisher A, Cavazzana-Calvo M Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity. Blood. 93:1999;3550-3557.
46. Jain RK Delivery of molecular medicine to solid tumors. Science. 271:1996;1079-1080.
47. Goldberg MR, Heimbrook DC, Russo P, Sarosdy MF, Greenberg RE, Giantonio BJ, Linehan WM, Walther M, Fisher HAG, Messing Eet al. Phase I clinical study of recombinant oncotoxin TP40 in superficial bladder cancer. Clin Cancer Res. 1:1995;57-61.
48. 389EGF are also given.
49. Lorimer IAJ, Wikstrand CJ, Batra SK, Bigner DD, Pastan I Immunotoxins that target an oncogenic mutant epidermal growth factor receptor expressed in human tumors. Clin Cancer Res. 1:1995;859-864.
50. Lorimer IA, Keppler-Hafkemeyer A, Beers RA, Pegram CN, Bigner DD, Pastan I Recombinant immunotoxins specific for a mutant epidermal growth factor receptor: targeting with a single chain antibody variable domain isolated by phage display. Proc Natl Acad Sci USA. 93:1996;14815-14820.
51. Pastan I, Lovelace ET, Gallo MG, Rutherford AV, Magnani JL, Willingham MC Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. Cancer Res. 51:1991;3781-3787.
52. Brinkmann U, Pai LH, FitzGerald DJ, Willingham M, Pastan I B3(Fv)-PE38KDEL, a single-chain immunotoxin that causes complete regression of a human carcinoma in mice. Proc Natl Acad Sci USA. 88:1991;8616-8620.
53. Siegall CB, Chace D, Mixan B, Garrigues U, Wan H, Paul L, Wolff E, Hellstrom I, Hellstrom KE In vitro and in vivo characterization of BR96 sFv-PE40. A single-chain immunotoxin fusion protein that cures human breast carcinoma xenografts in athymic mice and rats. J Immunol. 152:1994;2377-2384.
54. Laske DW, Muraszko KM, Oldfield EH, DeVroom HL, Sung C, Dedrick RL, Simon TR, Colandrea J, Copeland C, Katz Det al. Intraventricular immunotoxin therapy for leptomeningeal neoplasia. Neurosurgery. 41:1997;1039-1049.
55. Greenfield L, Johnson VG, Youle RJ Mutations in diphtheria toxin separate binding from entry and amplify immunotoxin selectivity. Science. 238:1987;536-539.
56. Puri RK, Leland P, Kreitman RJ, Pastan I Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein. Int J Cancer. 58:1994;574-581.
57. Kreitman RJ, Puri RK, Pastan I A circularly permuted recombinant interleukin 4 toxin with increased activity. Proc Natl Acad Sci USA. 91:1994;6889-6893.
58. Kreitman RJ, Puri RK, Pastan I Increased antitumor activity of a circularly permuted interleukin 4-toxin in mice with interleukin 4 receptor-bearing human carcinoma. Cancer Res. 55:1995;3357-3363.
59. Laske DW, Youle RJ, Oldfield EH Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med. 3:1997;1362-1368.
60. 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 Cancer. 8:1994;57-59.
61. Siegall CB, Haggerty HG, Warner GL, Chace D, Mixan B, Linsley PS, Davidson T Prevention of immunotoxin-induced immunogenicity by coadministration with CTLA4Ig enhances antitumor efficacy. J Immunol. 159:1997;5168-5173.
62. McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas Fet al. Rituximab chimeric Anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 16:1998;2825-2833.
63. Siegall CB, Liggitt D, Chace D, Mixan B, Sugai J, Davidson T, Steinitz M Characterization of vascular leak syndrome induced by the toxin component of Pseudomonas exotoxin-based immunotoxins and its potential inhibition with nonsteroidal anti-inflammatory drugs. Clin Cancer Res. 3:1997;339-345.
64. Siegall CB, Liggitt D, Chace D, Tepper MA, Fell HP Prevention of immunotoxin-mediated vascular leak syndrome in rats with retention of antitumor activity. Proc Natl Acad Sci USA. 91:1994;9514-9518.
65. Rozemuller H, Rombouts WJC, Touw IP, FitzGerald DJP, Kreitman RJ, Pastan I, Hagenbeek A, Martens ACM Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model. Leukemia. 10:1996;1796-1803.
66. Baluna R, Vitetta ES Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology. 37:1997;117-132.
67. Lindstrom AL, Erlandsen SL, Kersey JH, Pennell CA An in vitro model for toxin-mediated vascular leak syndrome: ricin toxin A chain increases the permeability of human endothelial cell monolayers. Blood. 90:1997;2323-2334.
68. Baluna R, Vitetta ES An in vivo model to study immunotoxin induced vascular leak in human tissue. J Immunother. 22:1999;41-47. Baluna and Vitetta performed skin grafting of foreskin or adult skin onto SCID mice and after systemic treatment of mice with immunotoxin measured changes in permeability via extravasation of Carbon Black or Evans Blue dye in the graft.
69. Baluna R, Rizo J, Gordon BE, Ghetie V, Vitetta ES 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. 96:1999;3957-3962. Baluna et al. identify a tripeptide motif in RTA (LDV, using single-letter code for amino acids) which causes VLS as assessed by the in vivo model of skin transplants in SCID mice and also mediates binding to HUVECs. Similar sequences - such as GDL and GDV (in PE38), LDL (in IL-2) and VDS, IDS and LDV (in DT) - were also identified.
70. Uchida T, Pappenheimer AM Jr., Harper AA Reconstitution of diphtheria toxin from two nontoxic cross-reacting mutant proteins. Science. 175:1972;901-903.
71. Uchida T, Pappenheimer AM Jr., Greany R Diphtheria toxin and related proteins I. Isolation and properties of mutant proteins serologically related to diphtheria toxin. J Biol Chem. 248:1973;3838-3844.
72. Iwamoto R, Higashiyama S, Mitamura T, Taniguchi N, Klagsbrun M, Mekada E Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J. 13:1994;2322-2330.
73. r ~ 6000 region of the toxin. J Biol Chem. 265:1990;7331-7337.
74. Kaul P, Silverman J, Shen WH, Blanke SR, Huynh PD, Finkelstein A, Collier RJ Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin. Protein Sci. 5:1996;687-692.
75. Hwang J, FitzGerald DJ, Adhya S, Pastan I Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell. 48:1987;129-136.
76. Allured VS, Collier RJ, Carroll SF, McKay DB Structure of exotoxin A of Pseudomonas aeruginosa at 3.0 Angstrom resolution. Proc Natl Acad Sci USA. 83:1986;1320-1324.
77. Ogata M, Chaudhary VK, Pastan I, FitzGerald DJ 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 Biol Chem. 265:1990;20678-20685.
78. 280 generates the enzymatically active fragment which translocates to the cytosol. J Biol Chem. 267:1992;25396-25401.
79. Endo Y, Mitsui K, Motizuki M, Tsurugi K The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. J Biol Chem. 262:1987;5908-5912.
80. Zamboni M, Brigotti M, Rambelli F, Montanaro L, Sperti S High pressure liquid chromatographic and fluorimetric methods for the determination of adenine released from ribosomes by ricin and gelonin. Biochem, J. 259:1989;639-643.
81. Carroll SF, Collier RJ 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. 262:1987;8707-8711.
82. Chiron MF, Fryling CM, FitzGerald DJ Cleavage of Pseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver. J Biol Chem. 269:1994;18167-18176.
83. Fryling C, Ogata M, FitzGerald D Characterization of a cellular protease that cleaves Pseudomonas exotoxin. Infect Immun. 60:1992;497-502.
84. 194. J Biol Chem. 265:1990;20673-20677.
85. Hessler JL, Kreitman RJ An early step in Pseudomonas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor. Biochemistry. 36:1997;14577-14582.
86. Kreitman RJ, 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. 307:1995;29-37.
87. vanderSpek J, Cassidy D, Genbauffe F, Huynh PD, Murphy JR An intact transmembrane helix 9 is essential for the efficient delivery of the diphtheria toxin catalytic domain to the cytosol of target cells. J Biol Chem. 269:1994;21455-21459.
88. Zhan H, Choe S, Huynh PD, Finkelstein A, Eisenberg D, Collier RJ Dynamic transitions of the transmembrane domain of diphtheria toxin: disulfide trapping and fluorescence proximity studies. Biochemistry. 33:1994;11254-11263.
89. Cabiaux V, Mindell J, Collier RJ Membrane translocation and channel-forming activities of diphtheria toxin are blocked by replacing isoleucine 364 with lysine. Infect Immun. 61:1993;2200-2202.
90. Brinkmann U, Brinkmann E, Gallo M, Pastan I Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1. Proc Natl Acad Sci USA. 92:1995;10427-10431.
91. Williams JM, Lea N, Lord JM, Roberts LM, Milford DV, Taylor CM Comparison of ribosome-inactivating proteins in the induction of apoptosis. Toxicol Lett. 91:1997;121-127.
92. Martin PJ, Nelson BJ, Appelbaum FR, Anasetti C, Deeg HJ, Hansen JA, McDonald GB, Nash RA, Sullivan KM, Witherspoon RPet al. Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Blood. 88:1996;824-830.
93. O'Toole JE, Esseltine D, Lynch TJ, Lambert JM, Grossbard ML Clinical trials with blocked ricin immunotoxins. Curr Top Microbiol Immunol. 234:1998;35-56.
94. Frankel AE, Laver JH, Willingham MC, Burns LJ, Kersey JH, Vallera DA Therapy of patients with T-cell lymphomas and leukemias using an anti-CD7 monoclonal antibody-ricin A chain immunotoxin. Leuk Lymphoma. 26:1997;287-298.
95. Kreitman RJ, Wilson WH, Robbins D, Margulies I, Stetler-Stevenson M, Waldmann TA, Pastan I Responses in refractory hairy cell leukemia to a recombinant immuntoxin. Blood. 1999;. in press.
96. Hall PD, Willingham MC, Kreitman RJ, Frankel AE DT388-GM-CSF, a novel fusion toxin consisting of a truncated diphtheria toxin fused to human granulocyte-macrophage colony stimulating factor, prolongs survival in a SCID model of acute myelogenous leukemia. Leukemia. 13:1999;629-633.
97. Lynch TJ, Lambert JM, Coral F, Shefner J, Wen P, Blattler WA, Collinson AR, Ariniello PD, Braman G, Cook Set al. Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin. J Clin Oncol. 15:1997;723-734.