Prospects of bacterial and plant protein-based immunotoxins for treatment of cancer

Cancer Genomics and Proteomics

Volumn 11, Issue 1, 2014, Pages 25-38

  Weidle, Ulrich H ^a   Tiefenthaler, Georg ^a   Schiller, Christian ^b   Weiss, Elisabeth H ^b   Georges, Guy ^a   Brinkmann, Ulrich ^a  

^a ROCHE INNOVATION CENTER MUNICH   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

Author keywords

Anthrax toxin; Deimmunization; Diphthamide; Diphtheria toxin; Eukaryotic elongation factor 2; Proof of concept studies; Pseudomonas exotoxin; Review; Ribosome inactivating proteins; Ricin; Saporin

Indexed keywords

ADENOSINE DIPHOSPHATE; ANTHRAX TOXIN; B CELL ACTIVATING FACTOR RECEPTOR; BACTERIAL TOXIN; CELL SURFACE RECEPTOR; COLONY STIMULATING FACTOR 1; COLONY STIMULATING FACTOR RECEPTOR; DENILEUKIN DIFTITOX; DIPHTHERIA TOXIN; GLYCOSIDASE; IMMUNOTOXIN; MITOGEN ACTIVATED PROTEIN KINASE; MOXETUMOMAB PASUDOTOX; MYELOID LEUKEMIA FACTOR 1; PLANT TOXIN; PSEUDOMONAS AERUGINOSA EXOTOXIN A; PSEUDOMONAS EXOTOXIN; RIBOSOME INACTIVATING PROTEIN BASED IMMUNOTOXIN; RICIN; SAPORIN; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2; ANTINEOPLASTIC AGENT; BACTERIAL PROTEIN; VEGETABLE PROTEIN;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADENOSINE DIPHOSPHATE RIBOSYLATION; ANTINEOPLASTIC ACTIVITY; ASSAY; B CELL LYMPHOMA; BACILLUS ANTHRACIS; CANCER THERAPY; CELL KILLING; CELL SURFACE; CHRONIC LYMPHATIC LEUKEMIA; CORYNEBACTERIUM DIPHTHERIAE; CYTOTOXICITY; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; ENZYME ACTIVE SITE; HAIRY CELL LEUKEMIA; HODGKIN DISEASE; HUMAN; IMMUNOGENICITY; IMMUNOTOXICITY; LARGE CELL LYMPHOMA; LIVER TOXICITY; NEOPLASM; NONHODGKIN LYMPHOMA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN SYNTHESIS; PSEUDOMONAS AERUGINOSA; REVIEW; TUMOR VASCULARIZATION; ANIMAL; NEOPLASMS;

ANIMALS; ANTINEOPLASTIC AGENTS; BACTERIAL PROTEINS; HUMANS; IMMUNOTOXINS; NEOPLASMS; PLANT PROTEINS;

EID: 84901423607     PISSN: 11096535     EISSN: 17906245     Source Type: Journal    
DOI: None     Document Type: Review

References (125)

1. Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell 144: 646-674, 2011.
2. Hanahan D and Coussens LM: Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell 21: 309-322, 2012.
3. Huang T, Karsy M, Zhuge J, Zhong M and Liu D: B-RAF and the inhibitors: from bench to bedside. J Hematol Oncol 6: 30, 2013.
4. Antonicelli A, Cafarotti S, Indini A, Galli A, Russo A, Cesario A, Lococo FM, Russo P, Mainini AF, Bonifati LG, Nosotti M, Santambrogio L, Margaritora S, Granone PM and Dutly AE: EGFR-targeted therapy for non-small cell lung cancer: Focus on EGFR oncogenic mutation. Int J Med Sci 10: 320-330, 2013.
5. Montoni A, Robu M, Pouliot E and Shah GM: Resistance to PARP-inhibitors in cancer therapy. Front Pharmacol 4: 18, 2013.
6. Weidle UH, Maisel D and Eick D: Synthetic lethality-based targets for discovery of new cancer therapeutics. Cancer Genomics Proteomics 8: 159-171, 2011.
7. Sennino B and McDonald DM: Controlling escape from angiogenesis inhibitors. Nat Rev Cancer 12: 699-709, 2012.
8. Jayson GC, Hicklin DJ and Ellis LM: Antiangiogenic therapy-evolving view based on clinical trial results. Nat Rev Clin Oncol 9: 297-303, 2012.
9. von Boehmer H and Daniel C: Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer. Nat Rev Drug Discov 12: 51-63, 2013.
10. Alderton GK and Bordon Y: Tumour immunotherapy leukocytes take up the fight. Nat Rev Immunol 12: 237, 2012.
11. Li F, Zhao C and Wang L: Molecular-targeted agents combination therapy for cancer: Developments and potentials. Int J Cancer, 2013, in press
12. Axelrod M, Gordon VL, Conaway M, Tarcsafalvi A, Neitzke DJ, Gioeli D and Weber MJ: Combinatorial drug screening identifies compensatory pathway interactions and adaptive resistance mechanisms. Oncotarget 4: 622-635, 2013.
13. Piro A, Tagarelli A, Tagarelli G, Lagonia P and Quattrone A: Paul Ehrlich: The Nobel Prize in physiology or medicine 1908. Int Rev Immunol 27: 1-17, 2008.
14. Shapira A and Benhar I: Toxin-based therapeutic approaches. Toxins 2: 2519-2583, 2010.
15. Ascenzi P, Visca P, Ippolito G, Spallarossa A, Bolognesi M and Montecucco C: Anthrax toxin: A tripartite lethal combination. FEBS Lett 531: 384-388, 2002. (Pubitemid 35336056)
16. Collier RJ and Young JA: Anthrax toxin. Annu Rev Cell Dev Biol 19: 45-70, 2003. (Pubitemid 37487342)
17. Young JA and Collier RJ: Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu Rev Biochem 76: 243-265, 2007.
18. Bradley KA, Mogridge J, Mourez M, Collier RJ and Young JA: Identification of the cellular receptor for anthrax toxin. Nature 414: 225-229, 2001. (Pubitemid 33051239)
19. Scobie HM, Rainey GJ, Bradley KA and Young JA: Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci USA 100: 5170-5174, 2003. (Pubitemid 36542677)
20. Adkins I, Holubova J, Kosova M and Sadilkova L: Bacteria and their toxins tamed for immunotherapy. Curr Pharm Biotechnol 13: 1446-1473, 2012.
21. Liu S, Netzel-Arnett S, Birkedal-Hansen H and Leppla SH: Tumor cell-selective cytotoxicity of matrix metalloproteinase-activated anthrax toxin. Cancer Res 60: 6061-6067, 2000.
22. Liu S, Wang H, Currie BM, Molinolo A, Leung HJ, Moayeri M, Basile JR, Alfano RW, Gutkind JS, Frankel AE, Bugge TH and Leppla SH: Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J Biol Chem 283: 529-540, 2008.
23. Alfano RW, Leppla SH, Liu S, Bugge TH, Meininger CJ, Lairmore TC, Mulne AF, Davis SH, Duesbery NS and Frankel AE: Matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis. Mol Cancer Res 7: 452-461, 2009.
24. Liu S, Bugge TH and Leppla SH: Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin. J Biol Chem 276: 17976-17984, 2001.
25. Liu S, Aaronson H, Mitola DJ, Leppla SH and Bugge TH: Potent antitumor activity of a urokinase-activated engineered anthrax toxin. Proc Natl Acad Sci USA 100: 657-662, 2003. (Pubitemid 36126108)
26. Duesbery NS, Resau J, Webb CP, Koochekpour S, Koo HM, Leppla SH and Vande Woude GF: Suppression of RAS-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways. Proc Natl Acad Sci USA 98: 4089-4094, 2001. (Pubitemid 32249903)
27. Depeille P, Young JJ, Boguslawski EA, Berghuis BD, Kort EJ, Resau JH, Frankel AE and Duesbery NS: Anthrax lethal toxin inhibits growth of and vascular endothelial growth factor release from endothelial cells expressing the human herpes virus 8 viral G protein coupled receptor. Clin Cancer Res 13: 5926-5934, 2007. (Pubitemid 47583921)
28. Endo Y, Mitsui K, Motizuki M and Tsurugi K: The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28-S ribosomal RNA caused by the toxins. J Biol Chem 262: 5908-5912, 1987.
29. Peumans WJ, Hao Q and Van Damme EJ: Ribosome-inactivating proteins from plants: More than RNA N-glycosidases? FASEB J 15: 1493-1506, 2001. (Pubitemid 32673379)
30. Girbés T, Ferreras JM, Arias FJ and Stirpe F: Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria. Mini Rev Med Chem 4: 461-476, 2004. (Pubitemid 38842607)
31. Hartley MR and Lord JM: Genetics of ribosome-inactivating proteins. Mini Rev Med Chem 4: 487-492, 2004. (Pubitemid 38842609)
32. Stirpe F: Ribosome-inactivating proteins. Toxicon 44: 371-383, 2004.
33. Nielsen K and Boston RS: Ribosome-inactivating proteins: A plant perspective. Annu Rev Plant Physiol Plant Mol Biol 52: 785-816, 2001. (Pubitemid 33720055)
34. Stone MJ, Sausville EA, Fay JW, Headlee D, Collins RH, Figg WD, Stetler-Stevenson M, Jain V, Jaffe ES, Solomon D, Lush RM, Senderowicz A, Ghetie V, Schindler J, Uhr JW and Vitetta ES: 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: 1188-1197, 1996. (Pubitemid 26276793)
35. Schnell R, Borchmann P, Staak JO, Schindler J, Ghetie V, Vitetta ES and Engert A: Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma. Ann Oncol 14: 729-736, 2003. (Pubitemid 36621773)
36. Schnell R, Staak O, Borchmann P, Schwartz C, Matthey B, Hansen H, Schindler J, Ghetie V, Vitetta ES, Diehl V and 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 Cancer Res 8: 1779-1786, 2002. (Pubitemid 34633735)
37. Polito L, Bortolotti M, Pedrazzi M and Bolognesi A: Immunotoxins and other conjugates containing saporin-s6 for cancer therapy. Toxins 3: 697-720, 2011.
38. Heisler I, Keller J, Tauber R, Sutherland M and Fuchs H: A cleavable adapter to reduce nonspecific cytotoxicity of recombinant immunotoxins. Int J Cancer 103: 277-282, 2003. (Pubitemid 35461522)
39. Rouleau C, Curiel M, Weber W, Smale R, Kurtzberg L, Mascarello J, Berger C, Wallar G, Bagley R, Honma N, Hasegawa K, Ishida I, Kataoka S, Thurberg BL, Mehraein K, Horten B, Miller G and Teicher BA: Endosialin protein expression and therapeutic target potential in human solid tumors: sarcoma versus carcinoma. Clin Cancer Res 14: 7223-7236, 2008.
40. Yang MY, Chaudhary A, Seaman S, Dunty J, Stevens J, Elzarrad MK, Frankel AE and St Croix B. The cell surface structure of tumor endothelial marker 8 (TEM8) is regulated by the actin cytoskeleton. Biochim Biophys Acta 1813: 39-49, 2011.
41. Rosenblum MG, Kohr WA, Beattie KL, Beattie WG, Marks W, Toman PD and Cheung L: Amino acid sequence analysis, gene construction, cloning, and expression of gelonin, a toxin derived from Gelonium multiflorum. J Interferon Cytokine Res 15: 547-555, 1995.
42. Mohamedali KA, Ran S, Gomez-Manzano C, Ramdas L, Xu J, Kim S, Cheung LH, Hittelman WN, Zhang W, Waltenberger J, Thorpe PE and Rosenblum MG: Cytotoxicity of VEGF(121)/ rGel on vascular endothelial cells resulting in inhibition of angiogenesis is mediated via VEGFR-2. BMC Cancer 11: 358, 2011.
43. Mohamedali KA, Li ZG, Starbuck MW, Wan X, Yang J, Kim S, Zhang W, Rosenblum MG and Navone NM: Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature. Clin Cancer Res 17: 2328-2338, 2011.
44. Lyu MA, Rai D, Ahn KS, Sung B, Cheung LH, Marks JW, Aggarwal BB, Aguiar RC, Gandhi V and Rosenblum MG: The rGel/BLyS fusion toxin inhibits diffuse large B-cell lymphoma growth in vitro and in vivo. Neoplasia 12: 366-375, 2010.
45. Lyu MA, Sung B, Cheung LH, Marks JW, Aggarwal BB, Aguiar RC and Rosenblum MG: The rGel/BLyS fusion toxin inhibits STAT3 signaling via down-regulation of interleukin-6 receptor in diffuse large B-cell lymphoma. Biochem Pharmacol 80: 1335-1342, 2010.
46. Cao Y, Marks JD, Marks JW, Cheung LH, Kim S and Rosenblum MG: Construction and characterization of novel, recombinant immunotoxins targeting the Her2/neu oncogene product: In vitro and in vivo studies. Cancer Res 69: 8987-8995, 2009.
47. Winkles JA: The TWEAK-Fn14 cytokine-receptor axis: Discovery, biology and therapeutic targeting. Nat Rev Drug Discov 7: 411-425, 2008.
48. Zhou H, Ekmekcioglu S, Marks JW, Mohamedali KA, Asrani K, Phillips KK, Brown SA, Cheng E, Weiss MB, Hittelman WN, Tran NL, Yagita H, Winkles JA and Rosenblum MG: The TWEAK receptor Fn14 is a therapeutic target in melanoma: immunotoxins targeting Fn14 receptor for malignant melanoma treatment. J Invest Dermatol 133: 1052-1062, 2013.
49. Cizeau J, Grenkow DM, Brown JG, Entwistle J and MacDonald GC: Engineering and biological characterization of VB6-845, an anti-EpCAM immunotoxin containing a T-cell epitope-depleted variant of the plant toxin bouganin. J Immunother 32: 574-584, 2009.
50. Potala S, Sahoo SK and Verma RS: Targeted therapy of cancer using diphtheria toxin-derived immunotoxins. Drug Discov Today 13: 807-815, 2008.
51. Liu S, Milne GT, Kuremsky JG, Fink GR and Leppla SH: Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. Mol Cell Biol 24: 9487-9497, 2004. (Pubitemid 39391685)
52. Frankel AE, Rossi P, Kuzel TM and Foss F: Diphtheria fusion protein therapy of chemoresistant malignancies. Curr Cancer Drug Targets 2: 19-36, 2002. (Pubitemid 34627376)
53. LeMaistre CF, Saleh MN, Kuzel TM, Foss F, Platanias LC, Schwartz G, Ratain M, Rook A, Freytes CO, Craig F, Reuben J and Nichols JC: Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood 91: 399-405, 1998. (Pubitemid 28053361)
54. 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 and Nichols J: Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol 19: 376-388, 2001. (Pubitemid 32112849)
55. Frankel AE, Hall PD, Burbage C, Vesely J, Willingham M, Bhalla K and Kreitman RJ: Modulation of the apoptotic response of human myeloid leukemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein. Blood 90: 3654-3661, 1997. (Pubitemid 27473436)
56. Kreitman RJ and 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: 252-259, 1997. (Pubitemid 27276569)
57. Todhunter DA, Hall WA, Rustamzadeh E, Shu Y, Doumbia SO and Vallera DA: A bispecific immunotoxin (DTAT13) targeting human IL-13 receptor (IL-13R) and urokinase-type plasminogen activator receptor (uPAR) in a mouse xenograft model. Protein Eng Des Sel 17: 157-164, 2004. (Pubitemid 38477742)
58. Stish BJ, Chen H, Shu Y, Panoskaltsis-Mortari A and Vallera DA: Increasing anticarcinoma activity of an anti-ERBB2 recombinant immunotoxin by the addition of an anti-EpCAM scFv. Clin Cancer Res 13: 3058-3067, 2007. (Pubitemid 46849583)
59. Allured VS, Collier RJ, Carroll SF and McKay DB: Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution. Proc Natl Acad Sci USA 83: 1320-1324, 1986. (Pubitemid 16016120)
60. Pastan I and FitzGerald D: Pseudomonas exotoxin: Chimeric toxins. J Biol Chem 264: 15157-15160, 1989. (Pubitemid 19242871)
61. Pastan I, Hassan R, Fitzgerald DJ and Kreitman RJ: Immunotoxin therapy of cancer. Nat Rev Cancer 6: 559-565, 2006. (Pubitemid 43980544)
62. Weldon JE and Pastan I: A guide to taming a toxin-recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancer. FEBS J 278: 4683-4700, 2011.
63. Wilson BA and Collier RJ: Diphtheria toxin and Pseudomonas aeruginosa exotoxin A: active-site structure and enzymic mechanism. Curr Top Microbiol Immunol 175: 27-41, 1992.
64. Foley BT, Moehring JM and Moehring TJ: Mutations in the elongation factor 2 gene which confer resistance to diphtheria toxin and Pseudomonas exotoxin A. Genetic and biochemical analyses. J Biol Chem 270: 23218-23225, 1995.
65. Ivankovic M, Rubelj I, Matulic M, Reich E and Brdar B: Site-specific mutagenesis of the histidine precursor of diphthamide in the human elongation factor-2 gene confers resistance to diphtheria toxin. Mutat Res 609: 34-42, 2006. (Pubitemid 44311619)
66. Jørgensen R, Merrill AR, Yates SP, Marquez VE, Schwan AL, Boesen T and Andersen GR: Exotoxin A eEF2 complex structure indicates ADP ribosylation by ribosome mimicry. Nature 436: 979-984, 2005. (Pubitemid 41191675)
67. Jørgensen R, Wang Y, Visschedyk D and Merrill AR: The nature and character of the transition state for the ADP-ribosyltransferase reaction. EMBO Rep 9: 802-809, 2008.
68. Keppler-Hafkemeyer A, Brinkmann U and Pastan I: Role of caspases in immunotoxin-induced apoptosis of cancer cells. Biochemistry 37: 16934-16942, 1998. (Pubitemid 28566770)
69. Keppler-Hafkemeyer A, Kreitman RJ and Pastan I: Apoptosis induced by immunotoxins used in the treatment of hematologic malignancies. Int J Cancer 87: 86-94, 2000. (Pubitemid 30368420)
70. Du X, Youle RJ, FitzGerald DJ and Pastan I: Pseudomonas exotoxin A-mediated apoptosis is Bak dependent and preceded by the degradation of Mcl-1. Mol Cell Biol 30: 3444-3452, 2010.
71. Kreitman RJ and Pastan I: Accumulation of a recombinant immunotoxin in a tumor in vivo: Fewer than 1000 molecules per cell are sufficient for complete responses. Cancer Res 58: 968-975, 1998. (Pubitemid 28182466)
72. Bard F, Mazelin L, Péchoux-Longin C, Malhotra V and Jurdic P: Src regulates Golgi structure and KDEL receptor-dependent retrograde transport to the endoplasmic reticulum. J Biol Chem 278: 46601-46606, 2003. (Pubitemid 37452235)
73. Yamaizumi M, Mekada E, Uchida T and Okada Y: One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell 15: 245-250, 1978. (Pubitemid 9027527)
74. Posey JA, Khazaeli MB, Bookman MA, Nowrouzi A, Grizzle WE, Thornton J, Carey DE, Lorenz JM, Sing AP, Siegall CB, LoBuglio AF and Saleh MN: A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors. Clin Cancer Res 8: 3092-3099, 2002. (Pubitemid 35155018)
75. Damle B, Tay L, Comereski C, Warner W and Kaul S: Influence of immunogenicity on the pharmacokinetics of BMS-191352, a Pseudomonas exotoxin immunoconjugate, in rats and dogs. J Pharm Pharmacol 52: 671-678, 2000. (Pubitemid 30410081)
76. Du X, Ho M and Pastan I: New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells. J Immunother 30: 607-613, 2007. (Pubitemid 47229695)
77. Baskar S, Wiestner A, Wilson WH, Pastan I and Rader C: Targeting malignant B-cells with an immunotoxin against ROR1. MAbs 4: 349-361, 2012.
78. Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, Yang L, Pickeral OK, Rassenti LZ, Powell J, Botstein D, Byrd JC, Grever MR, Cheson BD, Chiorazzi N, Wilson WH, Kipps TJ, Brown PO and Staudt LM: Relation of gene expression phenotype to immunoglobulin mutation genotype in B-cell chronic lymphocytic leukemia. J Exp Med 194: 1639-1647, 2001. (Pubitemid 33126814)
79. Klein U, Tu Y, Stolovitzky GA, Mattioli M, Cattoretti G, Husson H, Freedman A, Inghirami G, Cro L, Baldini L, Neri A, Califano A and Dalla-Favera R: Gene expression profiling of B-cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B-cells. J Exp Med 194: 1625-1638, 2001. (Pubitemid 33126813)
80. Tur MK, Huhn M, Jost E, Thepen T, Brümmendorf TH and Barth S: In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA in a human acute myeloid leukemia xenograft tumor model. Int J Cancer 129: 1277-1282, 2011.
81. Alderson RF, Kreitman RJ, Chen T, Yeung P, Herbst R, Fox JA and Pastan I: CAT-8015: a second-generation pseudomonas exotoxin A-based immunotherapy targeting CD22-expressing hematologic malignancies. Clin Cancer Res 15: 832-839, 2009.
82. Weldon JE, Xiang L, Zhang J, Beers R, Walker DA, Onda M, Hassan R and Pastan I. A recombinant immunotoxin against the tumor-associated antigen mesothelin reengineered for high activity, low off-target toxicity, and reduced antigenicity. Mol Cancer Ther 12: 48-57, 2013.
83. Godal A, Kumle B, Pihl A, Juell S and Fodstad O: Immunotoxins directed against the high-molecular-weight melanoma-associated antigen. Identification of potent antibody toxin combinations. Int J Cancer 52: 631-635, 1992.
84. Yazdi PT, Wenning LA and Murphy RM: Influence of cellular trafficking on protein synthesis inhibition of immunotoxins directed against the transferrin receptor. Cancer Res 55: 3763-3771, 1995.
85. Press OW, Martin PJ, Thorpe PE and Vitetta ES: Ricin A-chain containing immunotoxins directed against different epitopes on the CD2 molecule differ in their ability to kill normal and malignant T-cells. J Immunol 141: 4410-4417, 1988. (Pubitemid 19018236)
86. Decker T, Oelsner M, Kreitman RJ, Salvatore G, Wang QC, Pastan I, Peschel C and Licht T: Induction of caspase-dependent programmed cell death in B-cell chronic lymphocytic leukemia by anti-CD22 immunotoxins. Blood 103: 2718-2726, 2004. (Pubitemid 38393030)
87. Fitzgerald DJ, Moskatel E, Ben-Josef G, Traini R, Tendler T, Sharma A, Antignani A, Mussai F, Wayne A, Kreitman RJ and Pastan I: Enhancing immunotoxin cell-killing activity via combination therapy with ABT-737. Leuk Lymphoma 52: 79-81, 2011.
88. Du X, Xiang L, Mackall C and Pastan I: Killing of resistant cancer cells with low Bak by a combination of an antimesothelin immunotoxin and a TRAIL receptor 2 agonist antibody. Clin Cancer Res 17: 5926-5934, 2011.
89. Du X, Beers R, Fitzgerald DJ and Pastan I: Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activity. Cancer Res 68: 6300-6305, 2008.
90. Liu XF, FitzGerald DJ and Pastan I: The insulin receptor negatively regulates the action of Pseudomonas toxin-based immunotoxins and native Pseudomonas toxin. Cancer Res 73: 2281-2288, 2013.
91. Tortorella LL, Pipalia NH, Mukherjee S, Pastan I, Fitzgerald D and Maxfield FR: Efficiency of immunotoxin cytotoxicity is modulated by the intracellular itinerary. PLoS One 7: e47320, 2012.
92. Nagata S and Pastan I: Removal of B cell epitopes as a practical approach for reducing the immunogenicity of foreign protein-based therapeutics. Adv Drug Deliv Rev 61: 977-985, 2009.
93. Parker DC: T-Cell-dependent B-cell activation. Annu Rev Immunol 11: 331-360, 1993.
94. Bernard A, Coitot S, Brémont A and Bernard G: T- And B-cell cooperation: A dance of life and death. Transplantation 79: S8-S11, 2005. (Pubitemid 40293564)
95. Van Regenmortel MH: What is a B-cell epitope? Methods Mol Biol 524: 3-20, 2009.
96. Barlow DJ, Edwards MS and Thornton JM: Continuous and discontinuous protein antigenic determinants. Nature 322: 747-748, 1986. (Pubitemid 16074126)
97. Laver WG, Air GM, Webster RG and Smith-Gill SJ: Epitopes on protein antigens: Misconceptions and realities. Cell 61: 553-556, 1990.
98. De Groot AS, Knopp PM and Martin W: De-immunization of therapeutic proteins by T-cell epitope modification. Dev Biol 122: 171-194, 2005. (Pubitemid 43002219)
99. Parker DC: The functions of antigen recognition in T-cell-dependent B-cell activation. Semin Immunol 5: 413-420, 1993.
100. Onda M, Nagata S, FitzGerald DJ, Beers R, Fisher RJ, Vincent JJ, Lee B, Nakamura M, Hwang J, Kreitman RJ, Hassan R and 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 177: 8822-8834, 2006. (Pubitemid 44893849)
101. Nagata S, Numata Y, Onda M, Ise T, Hahn Y, Lee B and Pastan I: Rapid grouping of monoclonal antibodies based on their topographical epitopes by a label-free competitive immunoassay. J Immunol Methods 292: 141-155, 2004. (Pubitemid 39179870)
102. Onda M, Beers R, Xiang L, Nagata S, Wang QC and Pastan I: An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proc Natl Acad Sci USA 105: 11311-11316, 2008.
103. Onda M, Beers R, Xiang L, Lee B, Weldon JE, Kreitman RJ and Pastan I: Recombinant immunotoxin against B-cell malignancies with no immunogenicity in mice by removal of B-cell epitopes. Proc Natl Acad Sci USA 108: 5742-5747, 2011.
104. Liu W, Onda M, Lee B, Kreitman RJ, Hassan R, Xiang L and Pastan I: Recombinant immunotoxin engineered for low immunogenicity and antigenicity by identifying and silencing human B-cell epitopes. Proc Natl Acad Sci USA 109: 11782-11787, 2012.
105. Mazor R, Vassall AN, Eberle JA, Beers R, Weldon JE, Venzon DJ, Tsang KY, Benhar I and Pastan I: Identification and elimination of an immunodominant T-cell epitope in recombinant immunotoxins based on Pseudomonas exotoxin A. Proc Natl Acad Sci USA 109: E3597-3603, 2012.
106. Kreitman RJ and Pastan I: Antibody fusion proteins: Anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res 17: 6398-6405, 2011.
107. Kreitman RJ: Recombinant immunotoxins for the treatment of chemoresistant hematologic malignancies. Curr Pharm Des 15: 2652-2664, 2009.
108. Kreitman RJ, Margulies I, Stetler-Stevenson M, Wang QC, FitzGerald DJ and Pastan I: Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias. Clin Cancer Res 6: 1476-1487, 2000. (Pubitemid 30226237)
109. Kreitman RJ, Stetler-Stevenson M, Margulies I, Noel P, Fitzgerald DJ, Wilson WH and Pastan I: Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. J Clin Oncol 27: 2983-2990, 2009.
110. Salvatore G, Beers R, Margulies I, Kreitman RJ and Pastan I: Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. Clin Cancer Res 8: 995-1002, 2002. (Pubitemid 35177347)
111. Kelly RJ, Sharon E, Pastan I and Hassan R: Mesothelin-targeted agents in clinical trials and in preclinical development. Mol Cancer Ther 11: 517-525, 2012.
112. Chang K, Pastan I and Willingham MC: Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium. Int J Cancer 50: 373-381, 1992.
113. Chowdhury PS, Viner JL, Beers R and Pastan I: Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity. Proc Natl Acad Sci USA 95: 669-674, 1998. (Pubitemid 28083801)
114. Chowdhury PS and Pastan I: Improving antibody affinity by mimicking somatic hypermutation in vitro. Nat Biotechnol 17: 568-572, 1999. (Pubitemid 29262920)
115. Zhang Y, Xiang L, Hassan R, Paik CH, Carrasquillo JA, Jang BS, Le N, Ho M and Pastan I: Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice. Clin Cancer Res 12: 4695-4701, 2006. (Pubitemid 44297823)
116. Zhang Y, Xiang L, Hassan R and Pastan I: Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumors. Proc Natl Acad Sci USA 104: 17099-17104, 2007. (Pubitemid 350210998)
117. Hassan R, Sharon E, Schuler B, Mallory Y, Zhang Y, Ling A and Pastan I: Antitumor activity of SS1P with pemetrexed and cisplatin for front-line treatment of pleural mesothelioma and utility of serum mesothelin as a marker of tumor response. J Clin Oncol 29: 15S, (suppl; abstr 7026), 2011.
118. Kreitman RJ: Immunotoxins for targeted cancer therapy. AAPS J 8: E532-551, 2006.
119. Onda M, Nagata S, Tsutsumi Y, Vincent JJ, Wang Q, Kreitman RJ, Lee B and Pastan I: Lowering the isoelectric point of the Fv portion of recombinant immunotoxins leads to decreased nonspecific animal toxicity without affecting antitumor activity. Cancer Res 61: 5070-5077, 2001. (Pubitemid 32681537)
120. Pastan I, Hassan R, FitzGerald DJ and Kreitman RJ: Immunotoxin treatment of cancer. Annu Rev Med 58: 221-237, 2007. (Pubitemid 46706511)
121. Jeyarajah DR and Thistlethwaite JR Jr.: General aspects of cytokine-release syndrome: timing and incidence of symptoms. Transplant Proc 25: 16-20, 1993. (Pubitemid 23115816)
122. Pastan I, Lovelace ET, Gallo MG, Rutherford AV, Magnani JL and Willingham MC: Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. Cancer Res 51: 3781-3787, 1991.
123. Pai-Scherf LH, Villa J, Pearson D, Watson T, Liu E, Willingham MC and Pastan I: Hepatotoxicity in cancer patients receiving ERB-38, a recombinant immunotoxin that targets the ERBB2 receptor. Clin Cancer Res 5: 2311-2315, 1999. (Pubitemid 29437307)
124. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN and Bourne PE: The Protein Data Bank (www.pdb.org). Nucleic Acids Res 28: 235-242, 2000.
125. Accelrys Software Inc., Discovery Studio Modeling Environment, Release 4.0. Accelrys Software Inc., San Diego, 2013.