Single-chain antibody-based immunotoxins targeting her2/neu: Design optimization and impact of affinity on antitumor efficacy and off-target toxicity

Molecular Cancer Therapeutics

Volumn 11, Issue 1, 2012, Pages 143-153

  Cao, Yu ^b   Marks, James D ^a   Huang, Qian ^b   Rudnick, Stephen I ^c   Xiong, Chiyi ^b   Hittelman, Walter N ^b   Wen, Xiaoxia ^b   Marks, John W ^b   Cheung, Lawrence H ^b   Boland, Kim ^c   Li, Chun ^b   Adams, Gregory P ^c   Rosenblum, Michael G ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c FOX CHASE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GELONIN; HYBRID PROTEIN; IMMUNOTOXIN; SINGLE CHAIN VARIABLE FRAGMENT ANTIBODY RECOMBINANT GELONIN FUSION PROTEIN B1D3; SINGLE CHAIN VARIABLE FRAGMENT ANTIBODY RECOMBINANT GELONIN FUSION PROTEIN MH3 B1; SINGLE CHAIN VARIABLE FRAGMENT ANTIBODY RECOMBINANT GELONIN FUSION PROTEIN ML3 9; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN ANTIBODY COMPLEX; ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHAGY; BINDING AFFINITY; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; IN VITRO STUDY; IN VIVO STUDY; INTERNALIZATION; LIVER TOXICITY; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; TUMOR XENOGRAFT;

ANIMALS; ANTIBODY AFFINITY; ANTINEOPLASTIC AGENTS; HUMANS; IMMUNOTOXINS; MICE; MICE, NUDE; NEOPLASMS; RECEPTOR, ERBB-2; RIBOSOME INACTIVATING PROTEINS, TYPE 1; SINGLE-CHAIN ANTIBODIES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84862907829     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-11-0519     Document Type: Article

References (45)

1. Jain RK. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev 2001;46:149-68.
2. Markman B, Tabernero J. Monoclonal antibodies in solid tumours. Curr Clin Pharmacol 2010;5:160-5.
3. Kreitman RJ, Pastan I. Immunotoxins in the treatment of hematologic malignancies. Curr Drug Targets 2006;7:1301-11. (Pubitemid 44509694)
4. Beckman RA, Weiner LM, Davis HM. Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors. Cancer 2007;109:170-9. (Pubitemid 46106231)
5. Schaedel O, Reiter Y. Antibodies and their fragments as anti-cancer agents. Curr Pharm Des 2006;12:363-78.
6. Posey JA, Khazaeli MB, Bookman MA, Nowrouzi A, Grizzle WE, Thornton J, et al. A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors. Clin Cancer Res 2002;8:3092-9. (Pubitemid 35155018)
7. Smith SV. SGN-10. Seattle genetics. Curr Opin Investig Drugs 2001;2:1314-9.
8. Chaudhary VK, Queen C, Junghans RP, Waldmann TA, FitzGerald DJ, Pastan I. A recombinant immunotoxin consisting of two antibody variable-domains fusedtoPseudomonas exotoxin.Nature1989;339:394-7. (Pubitemid 19144230)
9. Powell DJ Jr, Felipe-Silva A, Merino MJ, Ahmadzadeh M, Allen T, Levy C, et al. 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;179:4919-28.
10. Pennell CA, Erickson HA. Designing immunotoxins for cancer therapy. Immunol Res 2002;25:177-91. (Pubitemid 34264103)
11. Kreitman RJ. Immunotoxins for targeted cancer therapy. AAPS J 2006;8:E532-51. (Pubitemid 44321317)
12. Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ. Immunotoxin therapy of cancer. Nat Rev Cancer 2006;6:559-65. (Pubitemid 43980544)
13. Adams GP, Schier R, McCall AM, Simmons HH, Horak EM, Alpaugh RK, et al. High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res 2001;61:4750-5. (Pubitemid 32691886)
14. Rudnick SI, Adams GP. Affinity and avidity in antibody-based tumor targeting. Cancer Biother Radiopharm 2009;24:155-61.
15. Zhang Y, Pastan I. High shed antigen levels within tumors: an additional barrier to immunoconjugate therapy. Clin Cancer Res 2008;14:7981-6.
16. Cao Y, Marks JD, Marks JW, Cheung LH, Kim S, Rosenblum MG. Construction and characterization of novel, recombinant immunotoxins targeting the Her2/neu oncogene product: in vitro and in vivo studies. Cancer Res 2009;69:8987-95.
17. Schier R, McCall A, Adams GP, Marshall KW, Merritt H, Yim M, et al. Isolation of picomolar affinity anti-c-erbB-2 single-chain Fv by molecular evolution of the complementarity determining regions in the center of the antibody binding site. J Mol Biol 1996;263:551-67. (Pubitemid 26382075)
18. Rosenblum MG, Cheung LH, Liu Y, Marks JW III. Design, expression, purification, and characterization, in vitro and in vivo, of an antimelanoma single-chain Fv antibody fused to the toxin gelonin. Cancer Res 2003;63:3995-4002. (Pubitemid 36917918)
19. Schier R, Marks JD, Wolf EJ, Apell G, Wong C, McCartney JE, et al. In vitro and in vivo characterization of a human anti-c-erbB-2 single-chain Fv isolated from a filamentous phage antibody library. Immunotechnology 1995;1:73-81.
20. Thorburn J, Horita H, Redzic J, Hansen K, Frankel AE, Thorburn A. Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Cell Death Differ 2009;16:175-83.
21. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J 2008;14:154-69.
22. Adams KE, Ke S, Kwon S, Liang F, Fan Z, Lu Y, et al. Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer. J Biomed Opt 2007;12:024017.
23. King CR, Fischer PH, Rando RF, Pastan I. The performance of e23(Fv) PEs, recombinant toxins targeting the erbB-2 protein. Semin Cancer Biol 1996;7:79-86. (Pubitemid 26148450)
24. Mazor Y, Noy R, Wels WS, Benhar I. chFRP5-ZZ-PE38, a large IgG-toxin immunoconjugate outperforms the corresponding smaller FRP5 (Fv)-ETA immunotoxin in eradicating ErbB2-expressing tumor xenografts. Cancer Lett 2007;257:124-35. (Pubitemid 47464703)
25. Chan SY, Gordon AN, Coleman RE, Hall JB, Berger MS, Sherman ML, et al. A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinum-sensitive recurrent epithelial ovarian carcinoma. Cancer Immunol Immunother 2003;52:243-8. (Pubitemid 36535284)
26. Zhang Y, Xiang L, Hassan R, Pastan I. Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumors. Proc Natl Acad Sci U S A 2007;104:17099-104. (Pubitemid 350210998)
27. Ackerman ME, Pawlowski D, Wittrup KD. Effect of antigen turnover rate and expression level on antibody penetration into tumor spheroids. Mol Cancer Ther 2008;7:2233-40.
28. Austin CD, De Maziere AM, Pisacane PI, van Dijk SM, Eigenbrot C, Sliwkowski MX, et al. Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin. Mol Biol Cell 2004;15:5268-82. (Pubitemid 39564723)
29. Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998;16:2659-71. (Pubitemid 28363029)
30. Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999;18:2241-51. (Pubitemid 29186925)
31. Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996;14:737-44.
32. Leary AF, Hanna WM, van de Vijver MJ, Penault-Llorca F, Ruschoff J, Osamura RY, et al. Value and limitations of measuring HER-2 extracellular domain in the serum of breast cancer patients. J Clin Oncol 2009;27:1694-705.
33. Wels W, Harwerth IM, Mueller M, Groner B, Hynes NE. Selective inhibition of tumor cell growth by a recombinant single-chain antibody- toxin specific for the erbB-2 receptor. Cancer Res 1992;52: 6310-7.
34. Pai-Scherf LH, Villa J, Pearson D, Watson T, Liu E, Willingham MC, et al. Hepatotoxicity in cancer patients receiving erb-38, a recombinant immunotoxin that targets the erbB2 receptor. Clin Cancer Res 1999;5:2311-5. (Pubitemid 29437307)
35. Azemar M, Djahansouzi S, Jager E, Solbach C, Schmidt M, Maurer AB, et al. Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibodytoxin targeted to ErbB2/HER2. Breast Cancer Res Treat 2003;82:155-64. (Pubitemid 37521971)
36. Onda M, Willingham M, Wang QC, Kreitman RJ, Tsutsumi Y, Nagata S, et al. 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;165:7150-6. (Pubitemid 32001191)
37. Onda M, Kreitman RJ, 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;163:6072-7.
38. Arribas J, Borroto A. Protein ectodomain shedding. Chem Rev 2002;102:4627-38.
39. Dello SP, Rovida E. Transmodulation of cell surface regulatory molecules via ectodomain shedding. Biol Chem 2002;383:69-83. (Pubitemid 34224029)
40. Ghetie MA, Ghetie V, Vitetta ES. Immunotoxins for the treatment of Bcell lymphomas. Mol Med 1997;3:420-7.
41. Bang S, Nagata S, Onda M, Kreitman RJ, Pastan I. HA22 (R490A) is a recombinant immunotoxin with increased antitumor activity without an increase in animal toxicity. Clin Cancer Res 2005;11:1545-50. (Pubitemid 40315239)
42. Mathew M, Verma RS. Humanized immunotoxins: a new generation of immunotoxins for targeted cancer therapy. Cancer Sci 2009;100: 1359-65.
43. Baluna R, Vitetta ES. Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology 1997;37:117-32. (Pubitemid 27471029)
44. Vallera DA, Panoskaltsis-Mortari A, Blazar BR. Renal dysfunction accounts for the dose limiting toxicity of DT390anti-CD3sFv, a potential new recombinant anti-GVHD immunotoxin. Protein Eng 1997;10:1071-6. (Pubitemid 28004654)
45. Brown J, Rasamoelisolo M, Spearman M, Bosc D, Cizeau J, Entwistle J, et al. Preclinical assessment of an anti-EpCAM immunotoxin: locoregional delivery provides a safer alternative to systemic administration. Cancer Biother Radiopharm 2009;24:477-87.