Fully human targeted cytotoxic fusion proteins: New anticancer agents on the horizon

Cancer Genomics and Proteomics

Volumn 9, Issue 3, 2012, Pages 119-133

  Weidle, Ulrich H ^a   Georges, Guy ^a   Brinkmann, Ulrich ^a  

^a ROCHE DIAGNOSTICS GMBH   (Germany)

Author keywords

Apoptosis inducing factor; Cellular trafficking; Cytotoxic enzyme effectors; Death receptors and corresponding ligands; Endosome escape; Granzymes; Immuno RNAses; Review; Tumor targeting

Indexed keywords

ANTINEOPLASTIC AGENT; ANTITRANSFERRIN RECEPTOR AVIDIN FUSION PROTEIN; APOMAB; APOPTOSIS INDUCING FACTOR BASED FUSION PROTEIN; CASPASE 6; CONATUMUMAB; DEATH ASSOCIATED PROTEIN KINASE FUSION PROTEIN; DEATH RECEPTOR LIGAND FUSION PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FAS LIGAND; FURIN; GRANZYME B FUSION PROTEIN; HYBRID PROTEIN; LBY 135; LEXATUMUMAB; MAPATUMUMAB; MONOCLONAL ANTIBODY; RANPIRNASE; TIGATUZUMAB; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER INHIBITION; CELL DEATH; CELL VIABILITY; COLORECTAL CANCER; CYTOTOXICITY; ENDOCYTOSIS; GENE EXPRESSION; HUMAN; IC 50; IMMUNOGENICITY; MESOTHELIOMA; NONHUMAN; REVIEW; SARCOMA; SURVIVAL TIME; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED PERIODIC SYNDROME; TUMOR VOLUME;

EID: 84862565311     PISSN: 11096535     EISSN: 17906245     Source Type: Journal    
DOI: None     Document Type: Review

References (126)

1. Cai J, Han S, Qing R, Liao D, Law B and Boulton ME: In pursuit of new anti-angiogenic therapies for cancer treatment. Front Biosci 16: 803-814, 2011.
2. Bagshawe KD. Targeting: the ADEPT story so far. Curr Drug Targets 10: 152-157, 2009.
3. Pastan I, Hassan R, FitzGerald DJ and Kreitman RJ: Immunotoxin treatment of cancer. Annu Rev Med 58: 221-237, 2007.
4. Potala S, Sahoo SK and Verma RS: Targeted therapy of cancer using diphtheria toxin-derived immunotoxins. Drug Discov Today 13: 807-815, 2008.
5. Kreitman RJ: Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies. BioDrugs 23: 1-13, 2009.
6. Lindsay MA: Peptide-mediated cell delivery: application in protein target validation. Curr Opin Pharmacol 2: 587-594, 2002.
7. Conner SD and Schmid SL: Regulated portals of entry into the cell. Nature 422: 37-44, 2003.
8. Doherty GJ and McMahon HT: Mechanisms of endocytosis. Annu Rev Biochem 78: 857-902, 2009.
9. Sabharanjak S, Sharma P, Parton RG and Mayor S: GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. Dev Cell 2: 411-423, 2002.
10. Mellman I: Endocytosis and molecular sorting. Annu Rev Cell Dev Biol 12: 575-625, 1996.
11. Vogelzang NJ, Porta C and Mutti L: New agents in the management of advanced mesothelioma. Semin Oncol 32: 336-350, 2005.
12. Pavlakis N and Vogelzang NJ: Ranpirnase an antitumour ribonuclease: its potential role in malignant mesothelioma. Expert Opin Biol Ther 6: 391-939, 2006.
13. Rybak SM, Arndt MA, Schirrmann T, Dúbel S and Krauss J: Ribonucleases and immunoRNases as anticancer drugs. Curr Pharm Des 15: 2665-2675, 2009.
14. Rybak SM, Arndt MA, Schirrmann T, Dúbel S and Krauss J: Ribonucleases and immunoRNases as anticancer drugs. Curr Pharm Des 15: 2665-2675, 2009.
15. Schirrmann T, Krauss J, Arndt MA, Rybak SM and Dúbel S: Targeted therapeutic RNases (ImmunoRNases). Expert Opin Biol Ther 9: 79-95, 2009.
16. Krauss J, Arndt MA, Dúbel S and Rybak SM: Antibody-targeted RNase fusion proteins (immunoRNases) for cancer therapy. Curr Pharm Biotechnol 9: 231-234, 2008.
17. Mathew M and Verma RS: Humanized immunotoxins: a new generation of immunotoxins for targeted cancer therapy. Cancer Sci 100: 1359-1365, 2009.
18. De Lorenzo C and D'Alessio G: Human anti-ErbB2 immunoagents-immunoRNases and compact antibodies. FEBS J 276: 1527-1535, 2009.
19. Andrady C, Sharma SK and Chester KA: Antibody-enzyme fusion proteins for cancer therapy. Immunotherapy 3: 193-211, 2011.
20. Rybak SM: Antibody-onconase conjugates: cytotoxicity and intracellular routing. Curr Pharm Biotechnol 9: 226-230, 2008.
21. Adams GP, McCartney JE, Tai MS, Oppermann H, Huston JS, Stafford WF 3rd, Bookman MA, Fand I, Houston LL and Weiner LM: Highly specific in vivo tumor targeting by monovalent and divalent forms of 741F8 anti-c-erbB-2 singlechain Fv. Cancer Res 53: 4026-4034, 1993.
22. Krauss J, Arndt MA, Vu BK, Newton DL, Seeber S and Rybak SM: Efficient killing of CD22+ tumor cells by a humanized diabody-RNase fusion protein. Biochem Biophys Res Commun 331: 595-602, 2005.
23. Arndt MA, Krauss J, Vu BK, Newton DL and Rybak SM: A dimeric angiogenin immunofusion protein mediates selective toxicity toward CD22+ tumor cells. J Immunother 28: 245-251, 2005.
24. Makarov AA and Ilinskaya ON: Cytotoxic ribonucleases: molecular weapons and their targets. FEBS Lett 540: 15-20, 2003.
25. Sorrentino S, Naddeo M, Russo A and D'Alessio G: Degradation of double-stranded RNA by human pancreatic ribonuclease: crucial role of noncatalytic basic amino acid residues. Biochemistry 42: 10182-10190, 2003.
26. Iordanov MS, Ryabinina OP, Wong J, Dinh TH, Newton DL, Rybak SM and Magun BE: Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase: evidence for cytotoxic mechanisms different from inhibition of protein synthesis. Cancer Res 60: 1983-1994, 2000.
27. Gelardi T, Damiano V, Rosa R, Bianco R, Cozzolino R, Tortora G, Laccetti P, D'Alessio G and De Lorenzo C: Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant tumours. Br J Cancer 102: 513-519, 2010.
28. Riccio G, Esposito G, Leoncini E, Contu R, Condorelli G, Chiariello M, Laccetti P, Hrelia S, D'Alessio G and De Lorenzo C: Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents. FASEB J 23: 3171-3178, 2009.
29. Borriello M, Laccetti P, Terrazzano G, D'Alessio G and De Lorenzo C: A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours. Br J Cancer 104: 1716-1723, 2011.
30. 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.
31. Hetzel C, Bachran C, Fischer R, Fuchs H, Barth S and Stócker M: Small cleavable adapters enhance the specific cytotoxicity of a humanized immunotoxin directed against CD64-positive cells. J Immunother 31: 370-376, 2008.
32. Kurschus FC and Jenne DE: Delivery and therapeutic potential of human granzyme B. Immunol Rev 235: 159-171, 2010.
33. Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT and Nicholson DW: A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 272: 17907-17911, 1997.
34. Smyth MJ, McGuire MJ and Thia KY: Expression of recombinant human granzyme B. A processing and activation role for dipeptidyl peptidase I. J Immunol 154: 6299-6305, 1995.
35. Pham CT and Ley TJ: Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA 96: 8627-8632, 1999.
36. Rosenblum MG and Barth S: Development of novel, highly cytotoxic fusion constructs containing granzyme B: unique mechanisms and functions. Curr Pharm Des 15: 2676-2692, 2009.
37. Thomas DA, Du C, Xu M, Wang X and Ley TJ: DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis. Immunity 12: 621-632, 2000.
38. Woo EJ, Kim YG, Kim MS, Han WD, Shin S, Robinson H, Park SY and Oh BH: Structural mechanism for inactivation and activation of CAD/DF40 in the apoptotic pathway. Mol Cell 14: 531-539, 2004.
39. Trapani JA, Jans DA, Jans PJ, Smyth MJ, Browne KA and Sutton VR: Efficient nuclear targeting of granzyme B and the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent. J Biol Chem 273: 27934-27938, 1998.
40. Lucken-Ardjomande S and Martinou JC: Granzyme A, a stealth killer in the mitochondrion. Cell 133: 568-570, 2008.
41. Kurschus FC, Kleinschmidt M, Fellows E, Dornmair K, Rudolph R, Lilie H and Jenne DE: Killing of target cells by redirected granzyme B in the absence of perforin. FEBS Lett 562: 87-92, 2004.
42. Dálken B, Giesúbel U, Knauer SK and Wels WS: Targeted induction of apoptosis by chimeric granzyme B fusion proteins carrying antibody and growth factor domains for cell recognition. Cell Death Differ 13: 576-585, 2006.
43. Liu Y, Cheung LH, Hittelman WN and Rosenblum MG: Targeted delivery of human pro-apoptotic enzymes to tumor cells: In vitro studies describing a novel class of recombinant highly cytotoxic agents. Mol Cancer Ther 2: 1341-1350, 2003.
44. Liu Y, Zhang W, Niu T, Cheung LH, Munshi A, Meyn RE Jr and Rosenblum MG: Targeted apoptosis activation with GrB/scFvMEL modulates melanoma growth, metastatic spread, chemosensitivity, and radiosensitivity. Neoplasia 8: 125-135, 2006.
45. Liu Y, Cheung LH, Thorpe P and Rosenblum MG: Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: directed apoptotic events in vascular endothelial cells. Mol Cancer Ther 2: 949-959, 2003.
46. Stahnke B, Thepen T, Stöcker M, Rosinke R, Jost E, Fischer R, Tur MK and Barth S: Granzyme B-H22(scFv), a human immunotoxin targeting CD64 in acute myeloid leukemia of monocytic subtypes. Mol Cancer Ther 7: 2924-2932, 2008.
47. Kanatani I, Lin X, Yuan X, Manorek G, Shang X, Cheung LH and Rosenblum MG and Howell SB: Targeting granzyme B to tumor cells using a yoked human chorionic gonadotropin. Cancer Chemother Pharmacol 68: 979-990, 2011
48. Zhao J, Zhang LH, Jia LT, Zhang L, Xu YM, Wang Z, Yu CJ, Peng WD, Wen WH, Wang CJ, Chen SY and Yang AG: Secreted antibody/granzyme B fusion protein stimulates selective killing of HER2-overexpressing tumor cells. J Biol Chem 279: 21343-21348, 2004.
49. Kurschus FC, Bruno R, Fellows E, Falk CS and Jenne DE: Membrane receptors are not required to deliver granzyme B during killer cell attack. Blood 105: 2049-2058, 2005.
50. Kurschus FC, Fellows E, Stegmann E and Jenne DE: Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis. Proc Natl Acad Sci USA 105: 13799-13804, 2008.
51. Medema JP, de Jong J, Peltenburg LT, Verdegaal EM, Gorter A, Bres SA, Franken KL, Hahne M, Albar JP, Melief CJ and Offringa R: Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci USA 98: 11515-11520, 2001.
52. Lin Y, Hupp TR and Stevens C: Death-associated protein kinase (DAPK) and signal transduction: additional roles beyond cell death. FEBS J 277: 48-57, 2010.
53. Bialik S and Kimchi A: The death-associated protein kinases: structure, function, and beyond. Annu Rev Biochem 75: 189-210, 2006.
54. Deiss LP, Feinstein E, Berissi H, Cohen O and Kimchi A: Identification of a novel serine/threonine kinase and a novel 15-kDa protein as potential mediators of the gamma interferoninduced cell death. Genes Dev 9: 15-30, 1995.
55. Shani G, Henis-Korenblit S, Jona G, Gileadi O, Eisenstein M, Ziv T, Admon A and Kimchi A: Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. EMBO J 20: 1099-1113, 2001.
56. Shohat G, Spivak-Kroizman T, Cohen O, Bialik S, Shani G, Berrisi H, Eisenstein M and Kimchi A: The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism. J Biol Chem 276: 47460-47467, 2001.
57. Kimchi A: A cell death-promoting kinase. Nat Struct Biol 8: 824-826, 2001.
58. Gozuacik D and Kimchi A: DAPK protein family and cancer. Autophagy 2: 74-79, 2006.
59. Tur MK, Neef I, Jáger G, Teubner A, Stócker M, Melmer G and Barth S: Immunokinases, a novel class of immunotherapeutics for targeted cancer therapy. Curr Pharm Des 15: 2693-2699, 2009.
60. Tur MK, Neef I, Jost E, Galm O, Jáger G, Stócker M, Ribbert M, Osieka R, Klinge U and Barth S: Targeted restoration of down-regulated DAPK2 tumor suppressor activity induces apoptosis in Hodgkin lymphoma cells. J Immunother 32: 431-441, 2009.
61. Tur MK, Huhn M, Jost E, Thepen T, Brúmmendorf TH and Barth S: In vivo efficacy of the recombinant anti-CD64 immunbotoxin H22(scFV)-ETA in a human acute myeloid leukemia xenografts tumor model. Int J Cancer 129: 1277-1282, 2011.
62. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM and Kroemer G: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397: 441-446, 1999.
63. Candé C, Vahsen N, Kouranti I, Schmitt E, Daugas E, Spahr C, Luban J, Kroemer RT, Giordanetto F, Garrido C, Penninger JM and Kroemer G: AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis. Oncogene 23: 1514-1521, 2004.
64. Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G and Wu H: DNA binding is required for the apoptogenic action of apoptosis inducing factor. Nat Struct Biol 9: 680-684, 2002.
65. Mahmud H, Dálken B and Wels WS: Induction of programmed cell death in ErbB2/HER2-expressing cancer cells by targeted delivery of apoptosis-inducing factor. Mol Cancer Ther 8: 1526-1535, 2009.
66. Yu CJ, Jia LT, Meng YL, Zhao J, Zhang Y, Qiu XC, Xu YM, Wen WH, Yao LB, Fan DM, Jin BQ, Chen SY and Yang AG: Selective proapoptotic activity of a secreted recombinant antibody/AIF fusion protein in carcinomas overexpressing HER2. Gene Ther 13: 313-320, 2006.
67. Straub CS: Targeting IAPs as an approach to anticancer therapy. Curr Top Med Chem 11: 291-316, 2011.
68. Xu YM, Wang LF, Jia LT, Qiu XC, Zhao J, Yu CJ, Zhang R, Zhu F, Wang CJ, Jin BQ, Chen SY and Yang AG: A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2-overexpressing tumors. J Immunol 173: 61-67, 2004.
69. Wang LF, Zhou Y, Xu YM, Qiu XC, Zhou BG, Wang F, Long H, Chen X, Yang TT, Ma BA, Fan QY and Yang AG: A caspase-6 and anti-HER2 antibody chimeric tumor-targeted proapoptotic molecule decreased metastasis of human osteosarcoma. Cancer Invest 27: 774-780, 2009.
70. Ng PP, Dela Cruz JS, Sorour DN, Stinebaugh JM, Shin SU, Shin DS, Morrison SL and Penichet ML: An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells. Proc Natl Acad Sci USA 99: 10706-10711, 2002.
71. Bodmer JL, Schneider P and Tschopp J: The molecular architecture of the TNF superfamily. Trends Biochem Sci 27: 19-26, 2002.
72. Muppidi JR, Tschopp J and Siegel RM: Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction. Immunity 21: 461-465, 2004.
73. French LE and Tschopp J: Protein-based therapeutic approaches targeting death receptors. Cell Death Differ 10: 117-223, 2003.
74. Gonzalvez F and Ashkenazi A: New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene 29: 4752-4765, 2010.
75. Ashkenazi A: Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2: 420-430, 2002.
76. Ashkenazi A: Directing cancer cells to self-destruct with proapoptotic receptor agonists. Nat Rev Drug Discov 7: 1001-1012, 2008.
77. Ashkenazi A, Holland P and Eckhardt SG: Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL). J Clin Oncol 26: 3621-3630, 2008.
78. Wilson NS, Dixit V and Ashkenazi A: Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 10: 348-355, 2009.
79. Ashkenazi A and Herbst RS: To kill a tumor cell: the potential of proapoptotic receptor agonists. J Clin Invest 118: 1979-1990, 2008.
80. Ashkenazi A: Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev 19: 325-331, 2008.
81. Kelley SK and Ashkenazi A: Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol 4: 333-339, 2004.
82. Varfolomeev EE and Ashkenazi A: Tumor necrosis factor: an apoptosis JuNKie? Cell 116: 491-497, 2004.
83. Wilson NS, Yang B, Yang A, Loeser S, Marsters S, Lawrence D, Li Y, Pitti R, Totpal K, Yee S, Ross S, Vernes JM, Lu Y, Adams C, Offringa R, Kelley B, Hymowitz S, Daniel D, Meng G and Ashkenazi A: An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19: 101-113, 2011.
84. Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K, Lee D, von Goetz M, Yee SF, Totpal K, Huw L, Katta V, Cavet G, Hymowitz SG, Amler L and Ashkenazi A: Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13: 1070-1077, 2007.
85. Gerspach J, Pfizenmaier K and Wajant H: Improving TNF as a cancer therapeutic: tailor-made TNF fusion proteins with conserved antitumor activity and reduced systemic side effects. Biofactors 35: 364-372, 2009.
86. Lejeune FJ and Rüegg C: Recombinant human tumor necrosis factor: an efficient agent for cancer treatment. Bull Cancer 93: E90-100, 2006.
87. ten Hagen TL, Seynhaeve AL and Eggermont AM: Tumor necrosis factor-mediated interactions between inflammatory response and tumor vascular bed. Immunol Rev 222: 299-315, 2008.
88. Wajant H, Gerspach J and Pfizenmaier K: Tumor therapeutics by design: targeting and activation of death receptors. Cytokine Growth Factor Rev 16: 55-76, 2005.
89. Ranges GE, Bombara MP, Aiyer RA, Rice GG and Palladino MA Jr.: Tumor necrosis factor-alpha as a proliferative signal for an IL-2-dependent T-cell line: strict species specificity of action. J Immunol 142: 1203-1208, 1989.
90. Ameloot P, Fiers W, De Bleser P, Ware CF, Vandenabeele P and Brouckaert P: Identification of tumor necrosis factor (TNF) amino acids crucial for binding to the murine p75 TNF receptor and construction of receptor-selective mutants. J Biol Chem 276: 37426-37430, 2001.
91. Curnis F, Sacchi A, Borgna L, Magni F, Gasparri A and Corti A: Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol 18: 1185-1190, 2000.
92. Sacchi A, Gasparri A, Gallo-Stampino C, Toma S, Curnis F and Corti A: Synergistic antitumor activity of cisplatin, paclitaxel, and gemcitabine with tumor vasculature-targeted tumor necrosis factor-alpha. Clin Cancer Res 12: 175-182, 2006.
93. Scherf U, Benhar I, Webber KO, Pastan I and Brinkmann U: Cytotoxic and antitumor activity of a recombinant tumor necrosis factor-B1(Fv) fusion protein on LeY antigen-expressing human cancer cells. Clin Cancer Res 2: 1523-1531, 1996.
94. Vassalli P: The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10: 411-452, 1992.
95. Qin Z, van Tits LJ, Buurman WA and Blankenstein T: Human lymphotoxin has at least equal antitumor activity in comparison to human tumor necrosis factor but is less toxic in mice. Blood 85: 2779-2785, 1995.
96. Qin Z and Blankenstein T: Tumor growth inhibition mediated by lymphotoxin: evidence of B lymphocyte involvement in the antitumor response. Cancer Res 55: 4747-4751, 1995.
97. Liu Y, Cheung LH, Marks JW and Rosenblum MG: Recombinant single-chain antibody fusion construct targeting human melanoma cells and containing tumor necrosis factor. Int J Cancer 108: 549-557, 2004.
98. Liu Y, Zhang W, Cheung LH, Niu T, Wu Q, Li C, Van Pelt CS and Rosenblum MG: The antimelanoma immunocytokine scFvMEL/TNF shows reduced toxicity and potent antitumor activity against human tumor xenografts. Neoplasia 8: 384-393, 2006.
99. Mortara L, Balza E, Sassi F, Castellani P, Carnemolla B, De Lerma Barbaro A, Fossati S, Tosi G, Accolla RS and Borsi L: Therapy-induced antitumor vaccination by targeting tumor necrosis factor alpha to tumor vessels in combination with melphalan. Eur J Immunol 37: 3381-3392, 2007.
100. Scanlan MJ, Raj BK, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, Old LJ and Rettig WJ: Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA 91: 5657-5661, 1994.
101. Wúest T, Gerlach E, Banerjee D, Gerspach J, Moosmayer D and Pfizenmaier K: TNF-Selectokine: a novel prodrug generated for tumor targeting and site-specific activation of tumor necrosis factor. Oncogene 21: 4257-4265, 2002.
102. Gerspach J, Múller D, Múnkel S, Selchow O, Nemeth J, Noack M, Petrul H, Menrad A, Wajant H and Pfizenmaier K: Restoration of membrane TNF-like activity by cell surface targeting and matrix metalloproteinase- mediated processing of a TNF prodrug. Cell Death Differ 13: 273-284, 2006.
103. Gerspach J, Németh J, Múnkel S, Wajant H and Pfizenmaier K: Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surface. Cancer Immunol Immunother 55: 1590-1600, 2006.
104. Swann PG, Tolnay M, Muthukkumar S, Shapiro MA, Rellahan BL and Clouse KA: Considerations for the development of therapeutic monoclonal antibodies. Curr Opin Immunol 20: 493-499, 2008.
105. Watermann I, Gerspach J, Lehne M, Seufert J, Schneider B, Pfizenmaier K and Wajant H: Activation of CD95L fusion protein prodrugs by tumor-associated proteases. Cell Death Differ 14: 765-774, 2007.
106. Schneider B, Múnkel S, Krippner-Heidenreich A, Grunwald I, Wels WS, Wajant H, Pfizenmaier K and Gerspach J: Potent antitumoral activity of TRAIL through generation of tumortargeted single-chain fusion proteins. Cell Death Dis, e68, 2010.
107. Krippner-Heidenreich A, Grunwald I, Zimmermann G, Kúhnle M, Gerspach J, Sterns T, Shnyder SD, Gill JH, Mánnel DN, Pfizenmaier K and Scheurich P: Single-chain TNF, a TNF derivative with enhanced stability and antitumoral activity. J Immunol 180: 8176-8183, 2008.
108. Koschny R, Walczak H and Ganten TM: The promise of TRAIL - potential and risks of a novel anticancer therapy. J Mol Med 85: 923-935, 2007.
109. Beutler BA, Milsark IW and Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol 135: 3972-3977, 1985.
110. Kelley SK, Harris LA, Xie D, Deforge L, Totpal K, Bussiere J and Fox JA: Preclinical studies to predict the disposition of APO2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: characterization of in vivo efficacy, pharmacokinetics, and safety. J Pharmacol Exp Ther 299: 31-38, 2001.
111. Yamamoto Y, Tsutsumi Y, Yoshioka Y, Nishibata T, Kobayashi K, Okamoto T, Mukai Y, Shimizu T, Nakagawa S, Nagata S and Mayumi T: Site-specific PEGylation of a lysine-deficient TNF-alpha with full bioactivity. Nat Biotechnol 21: 546-552, 2003.
112. Múller N, Schneider B, Pfizenmaier K and Wajant H: Superior serum half life of albumin tagged TNF ligands. Biochem Biophys Res Commun 396: 793-799, 2010.
113. Wyzgol A, Múller N, Fick A, Munkel S, Grigoleit GU, Pfizenmaier K and Wajant H: Trimer stabilization, oligomerization, and antibody-mediated cell surface immobilization improve the activity of soluble trimers of CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligand. J Immunol 183: 1851-1861, 2009.
114. Berg D, Lehne M, Múller N, Siegmund D, Múnkel S, Sebald W, Pfizenmaier K and Wajant H: Enforced covalent trimerization increases the activity of the TNF ligand family members TRAIL and CD95L. Cell Death Differ 14: 2021-2034, 2007.
115. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC and Lynch DH: Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5: 157-163, 1999.
116. Molineux G: Pegylation: engineering improved biopharmaceuticals for oncology. Pharmacotherapy 23: 3S-8S, 2003.
117. Benhar I, Wang QC, FitzGerald D and Pastan I: Pseudomonas exotoxin A mutants. Replacement of surface-exposed residues in domain III with cysteine residues that can be modified with polyethylene glycol in a site-specific manner. J Biol Chem 269: 13398-13404, 1994.
118. Kushner BH, Cheung IY, Kramer K, Modak S and Cheung NK: High-dose cyclophosphamide inhibition of humoral immune response to murine monoclonal antibody 3F8 in neuroblastoma patients: broad implications for immunotherapy. Pediatr Blood Cancer 48: 430-434, 2007.
119. Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S and Goldsmith SJ: Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol 23: 5696-5704, 2005.
120. De Groot AS, Knopp PM and Martin W: De-immunization of therapeutic proteins by T-cell epitope modification. Dev Biol 122: 171-194, 2005.
121. Tangri S, Mothé BR, Eisenbraun J, Sidney J, Southwood S, Briggs K, Zinckgraf J, Bilsel P, Newman M, Chesnut R, Licalsi C and Sette A: Rationally engineered therapeutic proteins with reduced immunogenicity. J Immunol 174: 3187-3196, 2005.
122. Laroche Y, Heymans S, Capaert S, De Cock F, Demarsin E and Collen D: Recombinant staphylokinase variants with reduced antigenicity due to elimination of B-lymphocyte epitopes. Blood 96: 1425-1432, 2000.
123. 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.
124. 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.
125. 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.
126. 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.