A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation

mAbs

Volumn 7, Issue 5, 2015, Pages 931-945

  Shen, Yang ^a   Zeng, Lin ^a   Novosyadlyy, Ruslan ^a   Forest, Amelie ^a   Zhu, Aiping ^a   Korytko, Andrew ^a   Zhang, Haifan ^a,b   Eastman, Scott W ^a   Topper, Michael ^a   Hindi, Sagit ^a   Covino, Nicole ^a   Persaud, Kris ^a   Kang, Yun ^a   Burtrum, Douglas ^a   Surguladze, David ^a   Prewett, Marie ^a   Chintharlapalli, Sudhakar ^a   Wroblewski, Victor J ^a   Shen, Juqun ^a   Balderes, Paul ^a   Zhu, Zhenping ^a   Snavely, Marshall ^a   Ludwig, Dale L ^a   more..

^a ELI LILLY AND COMPANY   (United States)

^b Kadmon Corporation LLC   (United States)

Author keywords

Angiogenesis; Antibody fusion; Bi functional antibody; Bispecific antibody; Degradation; IGF IR; Internalization; VEGF; VEGFR1; VEGFR2

Indexed keywords

ANTINEOPLASTIC AGENT; BI FUNCTIONAL ANTIBODY RECEPTOR DOMAIN FUSION MOLECULE WITH LIGAND CAPTURE; FCD2; I3D2; ID2; IMMUNOGLOBULIN G; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN KINASE B; SOMATOMEDIN C; UNCLASSIFIED DRUG; VASCULOTROPIN; BISPECIFIC ANTIBODY; HYBRID PROTEIN; IGF1R PROTEIN, HUMAN; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; SOMATOMEDIN RECEPTOR; VASCULOTROPIN A;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MIGRATION; CELL VIABILITY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DIFFERENTIAL SCANNING CALORIMETRY; DRUG MEGADOSE; DRUG TARGETING; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; HUMAN CELL; IMMUNOREACTIVITY; INTERNALIZATION; LOW DRUG DOSE; MOUSE; NONHUMAN; PROTEIN BINDING; PROTEIN CROSS LINKING; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; SIZE EXCLUSION CHROMATOGRAPHY; SOLUBILITY; SURFACE PLASMON RESONANCE; TUMOR GROWTH; UMBILICAL CORD; UMBILICAL VEIN ENDOTHELIAL CELL; ANIMAL; ANTAGONISTS AND INHIBITORS; ANTIBODY AFFINITY; DRUG SCREENING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOBLOTTING; IMMUNOPRECIPITATION; NEOPLASMS, EXPERIMENTAL; NUDE MOUSE; PROTEIN STABILITY;

ANIMALS; ANTIBODIES, BISPECIFIC; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ANTIBODY AFFINITY; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMANS; IMMUNOBLOTTING; IMMUNOPRECIPITATION; MICE; MICE, NUDE; MICROSCOPY, CONFOCAL; NEOPLASMS, EXPERIMENTAL; PROTEIN STABILITY; RECEPTORS, SOMATOMEDIN; RECOMBINANT FUSION PROTEINS; SURFACE PLASMON RESONANCE; VASCULAR ENDOTHELIAL GROWTH FACTOR A; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84954313711     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2015.1055442     Document Type: Article

References (45)

1. Chames P, Baty D. Bispecific antibodies for cancer therapy: the light at the end of the tunnel? mAbs 2009; 1:539-47; PMID:20073127; http://dx. doi. org/ 10. 4161/mabs. 1. 6. 10015
2. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Dis Today 2015; PMID:25728220
3. Linke R, Klein A, Seimetz D. Catumaxomab: clinical development and future directions. mAbs 2010; 2:129-36; PMID:20190561; http://dx. doi. org/10. 4161/ mabs. 2. 2. 11221
4. Dong J, Demarest SJ, Sereno A, Tamraz S, Langley E, Doern A, Snipas T, Perron K, Joseph I, Glaser SM, et al. Combination of two insulin-like growth factor-I receptor inhibitory antibodies targeting distinct epitopes leads to an enhanced antitumor response. Mol Cancer Ther 2010; 9:2593-604; PMID:20716637; http://dx. doi. org/10. 1158/1535-7163. MCT-09-1018
5. Lu D, Zhang H, Ludwig D, Persaud A, Jimenez X, Burtrum D, Balderes P, Liu M, Bohlen P, Witte L, et al. Simultaneous blockade of both the epidermal growth factor receptor and the insulin-like growth factor receptor signaling pathways in cancer cells with a fully human recombinant bispecific antibody. J Biol Chem 2004; 279:2856-65; PMID:14576153; http://dx. doi. org/10. 1074/jbc. M310132200
6. Jordan JL, Arndt JW, Hanf K, Li G, Hall J, Demarest S, Huang F, Wu X, Miller B, Glaser S, et al. Structural understanding of stabilization patterns in engineered bispecific Ig-like antibody molecules. Proteins 2009; 77:832-41; PMID:19626705; http://dx. doi. org/ 10. 1002/prot. 22502
7. Davis JH, Aperlo C, Li Y, Kurosawa E, Lan Y, Lo KM, Huston JS. SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Eng, Des Sel 2010; 23:195-202; http://dx. doi. org/10. 1093/protein/gzp094
8. Mabry R, Gilbertson DG, Frank A, Vu T, Ardourel D, Ostrander C, Stevens B, Julien S, Franke S, Meengs B, et al. A dual-targeting PDGFRbeta/VEGF-A molecule assembled from stable antibody fragments demonstrates anti-angiogenic activity in vitro and in vivo. mAbs 2010; 2:20-34; PMID:20065654; http://dx. doi. org/ 10. 4161/mabs. 2. 1. 10498
9. Mabry R, Lewis KE, Moore M, McKernan PA, Bukowski TR, Bontadelli K, Brender T, Okada S, Lum K, West J, et al. Engineering of stable bispecific antibodies targeting IL-17A and IL-23. Protein Eng Des Sel 2010; 23:115-27; http://dx. doi. org/ 10. 1093/protein/gzp073
10. Miller BR, Demarest SJ, Lugovskoy A, Huang F, Wu X, Snyder WB, Croner LJ, Wang N, Amatucci A, Michaelson JS, et al. Stability engineering of scFvs for the development of bispecific and multivalent antibodies. Protein Eng Des Sel 2010; 23:549-57; http://dx. doi. org/10. 1093/protein/gzq028
11. Schaefer G, Haber L, Crocker LM, Shia S, Shao L, Dowbenko D, Totpal K, Wong A, Lee CV, Stawicki S, et al. A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell 2011; 20:472-86; PMID:22014573; http://dx. doi. org/10. 1016/j. ccr. 2011. 09. 003
12. Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, et al. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat Biotechnol 2014; 32:191-8; PMID:24463572; http:// dx. doi. org/10. 1038/nbt. 2797
13. Von Kreudenstein TS, Escobar-Carbrera E, Lario PI, D'Angelo I, Brault K, Kelly J, Durocher Y, Baardsnes J, Woods RJ, Xie MH, et al. Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design. mAbs 2013; 5:646-54; PMID:23924797; http://dx. doi. org/ 10. 4161/mabs. 25632
14. Schaefer W, Regula JT, Bahner M, Schanzer J, Croasdale R, Durr H, Gassner C, Georges G, Kettenberger H, Imhof-Jung S, et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc Natl Acad Sci U S A 2011; 108:11187-92; PMID:21690412; http://dx. doi. org/10. 1073/pnas. 1019002108
15. Labrijn AF, Meesters JI, de Goeij BE, van den Bremer ET, Neijssen J, van Kampen MD, Strumane K, Verploegen S, Kundu A, Gramer MJ, et al. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proc Natl Acad Sci U S A 2013; 110:5145-50; PMID:23479652; http://dx. doi. org/10. 1073/ pnas. 1220145110
16. List T, Neri D. Immunocytokines: a review of molecules in clinical development for cancer therapy. Clin Pharmacol 2013; 5:29-45; PMID:23990735
17. Ferrara N. VEGF-A: a critical regulator of blood vessel growth. Eur Cytokine Netw 2009; 20:158-63; PMID:20167554
18. Gerber HP, Hillan KJ, Ryan AM, Kowalski J, Keller GA, Rangell L, Wright BD, Radtke F, Aguet M, Ferrara N. VEGF is required for growth and survival in neonatal mice. Development 1999; 126:1149-59; PMID:10021335
19. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23:1011-27; PMID:15585754; http://dx. doi. org/10. 1200/JCO. 2005. 06. 081
20. Senger DR, Van de Water L, Brown LF, Nagy JA, Yeo KT, Yeo TK, Berse B, Jackman RW, Dvorak AM, Dvorak HF. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Reviews 1993; 12:303-24; PMID:8281615; http://dx. doi. org/ 10. 1007/BF00665960
21. Claesson-Welsh L. Healing hemangiomas. Nat Med 2008; 14:1147-8; PMID:18989275; http://dx. doi. org/ 10. 1038/nm1108-1147
22. Wiesmann C, Fuh G, Christinger HW, Eigenbrot C, Wells JA, de Vos AM. Crystal structure at 1. 7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell 1997; 91:695-704; PMID:9393862; http://dx. doi. org/10. 1016/S0092-8674(00)80456-0
23. Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 2002; 99:11393-8; PMID:12177445; http://dx. doi. org/10. 1073/ pnas. 172398299
24. Burtrum D, Zhu Z, Lu D, Anderson DM, Prewett M, Pereira DS, Bassi R, Abdullah R, Hooper AT, Koo H, et al. A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Res 2003; 63:8912-21; PMID:14695208
25. Rowinsky EK, Youssoufian H, Tonra JR, Solomon P, Burtrum D, Ludwig DL. IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res 2007; 13:5549s-55s; PMID:17875788; http://dx. doi. org/10. 1158/1078-0432. CCR-07-1109
26. Yap TA, Olmos D, Molife LR, de Bono JS. Targeting the insulin-like growth factor signaling pathway: figitumumab and other novel anticancer strategies. Exp Opin Investig Drugs 2011; 20:1293-304; PMID:21777167; http://dx. doi. org/10. 1517/ 13543784. 2011. 602630
27. Li H, Adachi Y, Yamamoto H, Min Y, Ohashi H, Ii M, Arimura Y, Endo T, Lee CT, Carbone DP, et al. Insulin-like growth factor-I receptor blockade reduces tumor angiogenesis and enhances the effects of bevacizumab for a human gastric cancer cell line, MKN45. Cancer 2011; 117:3135-47; PMID:21264842; http:// dx. doi. org/10. 1002/cncr. 25893
28. Reinmuth N, Liu W, Fan F, Jung YD, Ahmad SA, Stoeltzing O, Bucana CD, Radinsky R, Ellis LM. Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer. Clin Cancer Res 2002; 8:3259-69; PMID:12374697
29. Spiliotaki M, Markomanolaki H, Mela M, Mavroudis D, Georgoulias V, Agelaki S. Targeting the insulin-like growth factor I receptor inhibits proliferation and VEGF production of non-small cell lung cancer cells and enhances paclitaxel-mediated anti-tumor effect. Lung Cancer 2011; 73:158-65; PMID:21190751; http://dx. doi. org/10. 1016/j. lungcan. 2010. 11. 010
30. Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL. Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 1999; 59:3915-8; PMID:10463582
31. Kim KW, Bae SK, Lee OH, Bae MH, Lee MJ, Park BC. Insulin-like growth factor II induced by hypoxia may contribute to angiogenesis of human hepatocellular carcinoma. Cancer Res 1998; 58:348-51; PMID:9443416
32. Harding TC, Long L, Palencia S, Zhang H, Sadra A, Hestir K, Patil N, Levin A, Hsu AW, Charych D, et al. Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer. Sci Transl Med 2013; 5:178ra39; PMID:23536011; http://dx. doi. org/10. 1126/scitranslmed. 3005414
33. Ferrara N, Chen H, Davis-Smyth T, Gerber HP, Nguyen TN, Peers D, ChisholmV, Hillan KJ, Schwall RH. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 1998; 4:336-40; PMID:9500609; http://dx. doi. org/10. 1038/nm0398-336
34. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999; 5:623-8; PMID:10371499; http://dx. doi. org/10. 1038/9467
35. Sullivan LA, Brekken RA. The VEGF family in cancer and antibody-based strategies for their inhibition. mAbs 2010; 2:165-75; PMID:20190566; http://dx. doi. org/10. 4161/mabs. 2. 2. 11360
36. Falcon BL, O'Clair B, McClure D, Evans GF, Stewart J, SwearingenML, Chen Y, Allard K, Lee LN, Neote K, et al. Development and characterization of a high-throughput in vitro cord formation model insensitive to VEGF inhibition. J Hematol Oncol 2013; 6:31; PMID:23622716; http://dx. doi. org/10. 1186/1756-8722-6-31
37. Rudge JS, Holash J, Hylton D, Russell M, Jiang S, Leidich R, Papadopoulos N, Pyles EA, Torri A, Wiegand SJ, et al. VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc Natl Acad Sci U S A 2007; 104:18363-70; PMID:18000042; http://dx. doi. org/10. 1073/pnas. 0708865104
38. Witte L, Hicklin DJ, Zhu Z, Pytowski B, Kotanides H, Rockwell P, Bohlen P. Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy. Cancer Metastasis Rev 1998; 17:155-61; PMID:9770111; http://dx. doi. org/ 10. 1023/A:1006094117427
39. Shen Y, Zeng L, Zhu A, Blanc T, Patel D, Pennello A, Bari A, Ng S, Persaud K, Kang YK, et al. Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity. mAbs 2013; 5:418-31; PMID:23567210; http://dx. doi. org/ 10. 4161/mabs. 24291
40. Yang Y, Zhang Y, Cao Z, Ji H, Yang X, Iwamoto H, Wahlberg E, Lanne T, Sun B, Cao Y. Anti-VEGF-and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci U S A 2013; 110:12018-23; PMID:23818623; http://dx. doi. org/ 10. 1073/pnas. 1301331110
41. Bogusz J, Majchrzak A, Medra A, Cebula-Obrzut B, Robak T, Smolewski P. Mechanisms of action of the anti-VEGF monoclonal antibody bevacizumab on chronic lymphocytic leukemia cells. Postepy Hig Med Dosw (Online) 2013; 67:107-18; PMID:23475487; http://dx. doi. org/10. 5604/17322693. 1038349
42. Stefanini MO, Wu FT, Mac Gabhann F, Popel AS. Increase of plasma VEGF after intravenous administration of bevacizumab is predicted by a pharmacokinetic model. Cancer Res 2010; 70:9886-94; PMID:21118974; http://dx. doi. org/10. 1158/0008-5472. CAN-10-1419
43. Bottos A, Martini M, Di Nicolantonio F, Comunanza V, Maione F, Minassi A, Appendino G, Bussolino F, Bardelli A. Targeting oncogenic serine/threonine-protein kinase BRAF in cancer cells inhibits angiogenesis and abrogates hypoxia. Proc Natl Acad Sci U S A 2012; 109:E353-9; PMID:22203991; http://dx. doi. org/ 10. 1073/pnas. 1105026109
44. Igawa T, Maeda A, Haraya K, Tachibana T, Iwayanagi Y, Mimoto F, Higuchi Y, Ishii S, Tamba S, Hironiwa N, et al. Engineered monoclonal antibody with novel antigen-sweeping activity in vivo. PloS one 2013; 8: e63236; PMID:23667591; http://dx. doi. org/10. 1371/ journal. pone. 0063236
45. Kang YK, Hamzik J, Felo M, Qi B, Lee J, Ng S, Liebisch G, Shanehsaz B, Singh N, Persaud K, et al. Development of a novel and efficient cell culture flocculation process using a stimulus responsive polymer to streamline antibody purification processes. Biotechnol Bioeng 2013; 110:2928-37; PMID:23740533; http:// dx. doi. org/10. 1002/bit. 24969