Evaluation of a Novel Hexavalent Humanized Anti-IGF-1R Antibody and Its Bivalent Parental IgG in Diverse Cancer Cell Lines

PLoS ONE

Volumn 7, Issue 8, 2012, Pages

  Chang, Chien Hsing ^a,b   Wang, Yang ^a   Trisal, Preeti ^a   Li, Rongxiu ^a   Rossi, Diane L ^a   Nair, Anju ^a   Gupta, Pankaj ^a   Losman, Michele ^a   Cardillo, Thomas M ^a   Rossi, Edmund A ^b   Goldenberg, David M ^a,b,c  

^a IMMUNOMEDICS INC   (United States)

^b IBC Pharmaceuticals Inc   (United States)

^c GARDEN STATE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEX HR1; HR1; IMMUNOGLOBULIN G; PROTEIN ANTIBODY; RAPAMYCIN; SOMATOMEDIN B; SOMATOMEDIN C RECEPTOR; SOMATOMEDIN C RECEPTOR ANTIBODY; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CANCER CELL CULTURE; CANCER INVASION; CELL GROWTH; CELL INVASION; CELL PROLIFERATION; CELL SURFACE; COLONY FORMATION; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG POTENCY; DRUG SYNTHESIS; EPITOPE MAPPING; FEMALE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RHABDOMYOSARCOMA; TUMOR XENOGRAFT;

ANIMALS; ANTIBODIES, BLOCKING; ANTINEOPLASTIC AGENTS; CADHERINS; CELL LINE, TUMOR; CELL PROLIFERATION; CHROMATOGRAPHY, GEL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CULTURE MEDIA, SERUM-FREE; DOWN-REGULATION; EPITOPES; FLOW CYTOMETRY; HUMANS; IMMUNOGLOBULIN G; LIGHT; MICE; MOLECULAR WEIGHT; NEOPLASM INVASIVENESS; NEOPLASMS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, IGF TYPE 1; SCATTERING, RADIATION; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TUMOR STEM CELL ASSAY; VIMENTIN;

MUS MUSCULUS; RUMEX;

EID: 84865644518     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0044235     Document Type: Article

References (67)

1. Baserga R, Hongo A, Rubini M, Prisco M, Valentinis B, (1997) The IGF-1 receptor in cell growth, transformation and apoptosis. Biochim Biophys Acta 1332: F105-F126.
2. Pollak MN, Schernhammer ES, Hankinsen SE, (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4: 505-518.
3. Pollak M, (2008) Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer 8: 915-928.
4. Pollak M, (2012) The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer 12: 159-169.
5. Adams TE, Epa VC, Garrett TPJ, Ward CW, (2000) Structure and function of the type I insulin-like growth factor receptor. Cell Mol Life Sci 57: 1050-1093.
6. Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, (2002) Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem 277: 39684-39695.
7. Gronborg M, Wulff BS, Rasmussen JS, Kjeldsen T, Gammeltoft S, (1993) Structure-function relationship of the insulin-like growth factor-I receptor tyrosine kinase. J. Biol Chem 268: 23435-23440.
8. Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, et al. (1999) Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis. Mol Cell Biol 19: 7203-7215.
9. Whittaker J, Groth AV, Mynarcik DC, Pluzek L, Gadsboll VL, et al. (2001) Alanine scanning mutagenesis of a type 1 insulin-like growth factor receptor ligand binding site. J Biol Chem 276: 43980-43986.
10. Sorensen H, Whittaker L, Hinrichsen J, Groth A, Whittaker J, (2004) Mapping of the insulin-like growth factor II binding site of the Type I insulin-like growth factor receptor by alanine scanning mutagenesis. FEBS Lett 565: 19-22.
11. Belfiore A, Frasca F, Pandini G, Sciacca L, Vigneri R, (2009) Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev 30: 586-623.
12. Belfiore A, (2007) The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. Curr Pharm Des 13: 671-86.
13. Chakravarti A, Loeffler JS, Dyson NJ, (2002) Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 62: 200-207.
14. Riedemann J, Sohail M, Macaulay VM, (2007) Dual silencing of the EGF and type 1 IGF receptors suggests dominance of IGF signaling in human breast cancer cells. Biochim Biophys Res Commun 355: 700-706.
15. Wilsbacher JL, Zhang Q, Tucker LA, Hubbard RD, Sheppard GS, et al. (2008) Insulin-like growth factor-1 receptor and ErbB kinase inhibitor combinations block proliferation and induce apoptosis through cyclin D1 reduction and Bax activation. J Biol Chem 283: 23721-23730.
16. Buck E, Gokhale PC, Koujak S, Brown E, Eyzaguirre A, et al. (2010) Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in Cancer. Mol Cancer Ther 9: 2652-64.
17. Ulaneta DB, Ludwig DL, Kahn CR, Douglas D, (2010) Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. Proc Natl Acad Sci USA 107: 10791-10798.
18. Desbois-Mouthon C, Baron A, Blivet-Van Eggelpo M-J, Fartoux F, Venot C, (2009) Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin Cancer Res 15: 5445-5456.
19. Huang F, Greer A, Hurlburt W, Han X, Hafezi R, et al. (2009) The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors. Cancer Res 69: 161-70.
20. Kull FC Jr, Jacobs S, Su Y-F, Svoboda ME, van Wyk JJ, et al. (1983) Monoclonal antibodies to receptors for insulin and somatomedin-C. J Biol Chem 259: 6561-6566.
21. Arteaga CL, Kitten LJ, Coronado EB, Jacobs S, Kull FC Jr, et al. (1989) Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice. J Clin Invest 84: 1418-1423.
22. Bohulaa EA, Playfordb MP, Macaulaya VM, (2003) Targeting the type 1 insulin-like growth factor receptor as anti-cancer treatment. Anti-Cancer Drugs 14: 669-682.
23. Hofmann F, García-Echeverría C, (2005) Blocking insulin-like growth factor-I receptor as a strategy for targeting cancer. Drug Discov Today 10: 1041-1047.
24. Riedemann J, Macaulay VM, (2006) IGF1R signalling and its inhibition. Endocr Relat Cancer 13: S33-S43.
25. Sachdev D, Yee D, (2007) Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther 6: 1-12.
26. Chitnis MM, Yuen JSP, Protheroe AS, Pollak M, Macaulay VM, (2008) The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res 14: 6364-6370.
27. Rodon J, DeSantos V, Ferry RJ Jr, Kurzrock R, (2008) Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: lessons from the first clinical trials. Mol Cancer Ther 7: 2575-88.
28. Gualberto A, Pollak M, (2009) Emerging role of insulin-like growth factor receptor inhibitors in oncology: early clinical trial results and future directions. Oncogene 28: 3009-3021.
29. Hewish M, Chau I, Cunningham D, (2009) Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Recent Pat Anticancer Drug Discov 4: 54-72.
30. Kim SY, Toretsky JA, Scher D, Hellman LJ, (2009) The role of IGF-1R in pediatric malignancies. Oncologist 14: 83-91.
31. Werner H, Bruchim I, (2009) The insulin-like growth factor-I receptor as an oncogene. Arch Physiol Biochem 115: 58-71.
32. Robert G, Maki RG, (2010) Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J Clin Oncol 28: 4985-4995.
33. Olmos D, Tan DSW, Jones RL, Judson IR, (2010) Biological rationale and current clinical experience with anti-Insulin-like growth factor 1 receptor monoclonal antibodies in treating sarcoma: twenty years from the bench to the bedside. Cancer J 16: 183-194.
34. Zha J, Lackner MR, (2010) Targeting the insulin-like growth factor receptor-1R pathway for cancer therapy. Clin Cancer Res 16: 2512-2517.
35. Pollak M, (2012) The insulin receptor/insulin-like growth factor receptor family as a therapeutic target in oncology. Clin Cancer Res 18: 40-50.
36. Gao J, Chang YS, Jallal B, Viner J, (2012) Targeting the insulin-like growth factor axis for the development of novel therapeutics in oncology. Cancer Res 72: 3-12.
37. Gao J, Chesebrough JW, Cartlidge SA, Ricketts SA, Incognito L, et al. (2011) Dual IGF-I/II-neutralizing antibody MEDI-573 potently inhibits IGF signaling and tumor growth. Cancer Res 71: 1029-40.
38. Shang Y, Mao Y, Batson J, Scales SJ, Phillips G, et al. (2008) Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake. Mol Cancer Ther 7: 2599-2608.
39. Sachdev D, Singh R, Fujita-Yamaguchi Y, Yee D, (2006) Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer. Cancer Res 66: 2391-2402.
40. Karp DD, Paz-Ares LG, Novello S, Haluska P, Garland L, et al. (2009) Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Oncol 27: 2516-2522.
41. Gualberto A, Hixon ML, Karp DD, Li D, Green S, et al. (2011) Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab. Br J Cancer 104: 68-74.
42. Jassem J, Langer CJ, Karp DD, Mok T, Benner RJ, et al. (2010) Randomized, open label, phase III trial of figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). J Clin Oncol (Meet Abstr) 28(Suppl 15): 7500.
43. Moreau P, Cavallo F, Leleu X, Hulin C, M Amiot M, et al. (2011) Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma. Leukemia 25: 872-874.
44. Chang CH, Rossi EA, Goldenberg DM (2007) The dock and lock method: a novel platform technology for building multivalent, multifunctional structures of defined composition with retained bioactivity. Clin Cancer Res 13 (19 Suppl): 5586s-5591s.
45. Rossi EA, Goldenberg DM, Chang CH, (2012) The Dock-and-Lock method combines recombinant engineering with site-specific covalent conjugation to generate multifunctional structures. Bioconjugate Chem 23: 309-323.
46. Soos MA, Field CE, Lammers R, Ullrich A, Zhang B, et al. (1992) A panel of monoclonal antibodies for the type I insulin-like growth factor receptor. Epitope mapping, effects on ligand binding, and biological activity. J Biol Chem 267: 12955-12963.
47. Keyhanfar M, Booker GW, Whittaker J, Wallace JC, Forbes BE, (2007) Precise mapping of an IGF-I-binding site on the IGF-1R. Biochem J 401: 269-77.
48. Qu Z, Griffiths GL, Wegener WA, Chang CH, Govindan SV, et al. (2005) Development of humanized antibodies as cancer therapeutics. Methods 36: 84-95.
49. Rossi DL, Rossi EA, Goldenberg DM, Chang CH, (2011) A new mammalian host cell with enhanced survival enables completely serum-free development of high-level protein production cell lines. Biotechnol Prog 27: 766-775.
50. Rossi EA, Goldenberg DM, Cardillo TM, Stein R, Wang Y, et al. (2008) Novel designs of multivalent anti-CD20 humanized antibodies as improved lymphoma therapeutics. Cancer Res 68: 8384-8392.
51. Cao L, Yu Y, Darko I, Currier D, Mayeenuddin LH, et al. (2008) Addiction to elevated insulin-like growth factor I receptor and initial modulation of the AKT pathway define the responsiveness of rhabdomyosarcoma to the targeting antibody. Cancer Res 68: 8039-8048.
52. Hailey J, Maxwell E, Koukouras K, Bishop WR, Pachter JA, et al. (2002) Neutralizing anti-insulin-like growth factor receptor 1 antibodies Inhibit receptor function and induce receptor degradation in tumor cells. Mol Cancer Ther 1: 1349-1353.
53. Zha J, O'Brien C, Savage H, Huw L-Y, Zhong F, et al. (2009) Molecular predictors of response to a humanized anti-insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer. Mol Cancer Ther 8: 2110-2121.
54. Gong Y, Yao E, Shen R, Goel A, Arcila M, et al. (2009) High expression levels of total IGF-1R and sensitivity of NSCLC Cells in vitro to an anti-IGF-1R antibody (R1507). PLoS ONE 4: e7273.
55. Sachdev D, Li S-L, Hartell JS, Fujita-Yamaguchi Y, Miller JS, et al. (2003) A chimeric humanized single-chain antibody against the type I insulin-like growth factor (IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I. Cancer Res 63: 627-635.
56. Xiong L, Kasuya J, Li S-L, Kato J, Fujita-Yamaguchi Y, (1992) Growth-stimulatory monoclonal antibodies against human insulin-like growth factor I receptor. Proc Natl Acad Sci USA 89: 5356-5360.
57. Arteaga CL, Osborne CK, (1989) Growth inhibition of human breast cancer cell in vitro with an antibody against the type I somatomedin receptor. Cancer Res 49: 6237-6241.
58. Li S-I, Kato J, Paz B, Kasuya J, Fujita-Yamaguchi Y, (1992) Two new monoclonal antibodies against the α subunit of the human insulin-like growth factor-1 receptor. Biochem Biophys Res Commun 196: 92-98.
59. Burtrum D, Zhu Z, Lu D, Anderson DM, Prewett M, et al. (2003) A fully human monoclona antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Res 63: 8912-8921.
60. Keyhanfar M, Booker GW, Whittaker J, Wallace JC, Forbes BE, (2007) Precise mapping of an IGF-1-binding site on IGF-1R. Biochem J 401: 269-277.
61. Sachdev D, Zhang X, Matise I, Gaillard-Kelly M, Yee D, (2010) The type I insulin growth factor-like receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival. Oncogene 29: 251-262.
62. Rossi EA, Goldenberg DM, Cardillo TM, Stein R, Chang CH, (2009) Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma. Blood 113: 6161-6171.
63. Dong J, Demarest SJ, Sereno A, Tamraz S, Langley E, et al. (2010) Combination of two insulin-like growth factor-I receptor inhibitory antibodies targeting distinct epitopes leads to an enhanced antitumor response. Mol Cancer Ther 9: 2593-2604.
64. Dong J, Sereno A, Snyder WB, Miller BR, Tamraz S, et al. (2011) Stable IgG-like bispecific antibodies directed toward the type I Insulin-like growth factor receptor demonstrate enhanced ligand blockade and anti-tumor activity. J Biol Chem 286: 4703-4717.
65. Croasdale R, Wartha K, Schanzer JM, Klaus-Peter Kuenkele K-P, Ries C, et al. (2012) Development of tetravalent IgG1 dual targeting IGF-1R-EGFR antibodies with potent tumor inhibition. Arch Biochem Biophys March 21 [Epub ahead of print].
66. Chang CH, Rossi EA, Sharkey RM, Goldenberg DM (2011). The Dock-and-Lock (DNL) approach to novel bispecific antibodies. In R. E. Kontermann, ed. Bispecific Antibodies. Springer-Verlag Berlin Heidelberg: 199-216 (Ch. 12).
67. Wang Y, Trisal P, Cardillo TM, Rossi EA, Goldenberg DM, et al. (2012) Bispecific, hexavalent antibodies (HexAbs) targeting IGF-1R and either Trop-2 or CEACAM6 inhibit anchorage-independent growth and invasion of antigen-expressing breast and pancreatic cancer cell lines in vitro. AACR meeting abstract # 2727.