RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation

Cancer Research

Volumn 73, Issue 16, 2013, Pages 5183-5194

  Mirschberger, Christian ^a   Schiller, Christian B ^b   Schraml, Michael ^a   Dimoudis, Nikolaos ^a   Friess, Thomas ^a   Gerdes, Christian A ^c   Reiff, Ulrike ^a   Lifke, Valeria ^a   Hoelzlwimmer, Gabriele ^a   Kolm, Irene ^a   Hopfner, Karl Peter ^b   Niederfellner, Gerhard ^a   Bossenmaier, Birgit ^a  

^a ROCHE DIAGNOSTICS GMBH   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c Roche Glycart   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR 3; IMGATUZUMAB; MONOCLONAL ANTIBODY; NEU DIFFERENTIATION FACTOR; PERTUZUMAB; PROTEIN KINASE B; RG 7116; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ARTICLE; BINDING AFFINITY; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CANCER SURVIVAL; CONTROLLED STUDY; DIMERIZATION; DOSE RESPONSE; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; FEMALE; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LOADING DRUG DOSE; LUNG CANCER; LUNG NON SMALL CELL CANCER; MOUSE; MULTIPLE CYCLE TREATMENT; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RECEPTOR DOWN REGULATION; TUMOR XENOGRAFT;

EID: 84882679616     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-0099     Document Type: Article

References (49)

1. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 2004;59:21-6.
2. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341-54.
3. Sierke SL, Cheng K, Kim HH, Koland JG. Biochemical characterization of the protein tyrosine kinase homology domain of the ErbB3 (HER3) receptor protein. Biochem J 1997;322(Pt 3):757-63.
4. Berger MB, Mendrola JM, Lemmon MA. ErbB3/HER3 does not homodimerize upon neuregulin binding at the cell surface. FEBS Lett 2004;569:332-6.
5. Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, et al. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 1994;269: 14661-5.
6. Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 1996;16:5276-87.
7. Way TD, Lin JK. Role of HER2/HER3 co-receptor in breast carcinogenesis. Future Oncol 2005;1:841-9.
8. Vijapurkar U, Kim MS, Koland JG. Roles of mitogen-activated protein kinase and phosphoinositide 30-kinase in ErbB2/ErbB3 coreceptormediated heregulin signaling. Exp Cell Res 2003;284:291-302.
9. Ram TG, Ethier SP. Phosphatidylinositol 3-kinase recruitment by p185erbB-2 and erbB-3 is potently induced by neu differentiation factor/heregulin during mitogenesis and is constitutively elevated in growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification. Cell Growth Differ 1996;7:551-61.
10. Beji A, Horst D, Engel J, Kirchner T, Ullrich A. Toward the prognostic significance and therapeutic potential of HER3 receptor tyrosine kinase in human colon cancer. Clin Cancer Res 2012;18:956-68.
11. Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res 2008;68:5878-87.
12. Funayama T, Nakanishi T, Takahashi K, Taniguchi S, Takigawa M, Matsumura T. Overexpression of c-erbB-3 in various stages of human squamous cell carcinomas. Oncology 1998;55:161-7.
13. Koumakpayi IH, Diallo JS, Le PC, Lessard L, Gleave M, Begin LR, et al. Expression and nuclear localization of ErbB3 in prostate cancer. Clin Cancer Res 2006;12:2730-7.
14. Ocana A, Vera-Badillo F, Seruga B, Templeton A, Pandiella A, Amir E. HER3 overexpression and survival in solid tumors: a meta-analysis. J Natl Cancer Inst 2013;105:266-73.
15. Wheeler DL, Huang S, Kruser TJ, Nechrebecki MM, Armstrong EA, Benavente S, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene 2008;27: 3944-56.
16. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006;3:269-80.
17. Kruser TJ, Wheeler DL. Mechanisms of resistance to HER family targeting antibodies. Exp Cell Res 2010;316:1083-100.
18. Sergina NV, Rausch M, Wang D, Blair J, Hann B, Shokat KM, et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007;445:437-41.
19. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-43.
20. Alvarenga ML, Kikhney J, Hannewald J, Metzger AU, Steffens KJ, Bomke J, et al. In-depth biophysical analysis of interactions between therapeutic antibodies and the extracellular domain of the epidermal growth factor receptor. Anal Biochem 2012;421:138-51.
21. Schmiedel J, Blaukat A, Li S, Knochel T, Ferguson KM. Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization. Cancer Cell 2008;13:365-73.
22. Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005;7:301-11.
23. Li S, Kussie P, Ferguson KM. Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8. Structure 2008;16: 216-27.
24. Lammerts van Bueren JJ, Bleeker WK, BrannstromA, von EA, Jansson M, Peipp M, et al. The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility. Proc Natl Acad Sci U S A 2008;105:6109-14.
25. Bibeau F, Lopez-Crapez E, Di FF, Thezenas S, Ychou M, Blanchard F, et al. Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 2009;27:1122-9.
26. Schneider-Merck T, Lammerts van Bueren JJ, Berger S, Rossen K, van Berkel PH, Derer S, et al. Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage. J Immunol 2010;184:512-20.
27. Wright A, Morrison SL. Effect of glycosylation on antibody function: implications for genetic engineering. Trends Biotechnol 1997;15:26-32.
28. Niwa R, Sakurada M, Kobayashi Y, Uehara A, Matsushima K, Ueda R, et al. Enhanced natural killer cell binding and activation by low-fucose IgG1antibodyresults in potent antibody-dependent cellular cytotoxicity induction at lower antigen density. Clin Cancer Res 2005;11:2327-36.
29. Schlaeth M, Berger S, Derer S, Klausz K, Lohse S, Dechant M, et al. Fcengineered EGF-R antibodies mediate improved antibody-dependent cellular cytotoxicity (ADCC) against KRAS-mutated tumor cells. Cancer Sci 2010;101:1080-8.
30. Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature 1988;332:323-7.
31. Brunker P, Sondermann P, Umana P. Glycoengineered therapeutic antibodies. In:Little M, editor. Recombinant antibodies for immunotherapy. New York: Cambridge Univeristy Press; 2009. p. 144-56.
32. Ferrara C, Brunker P, Suter T, Moser S, Puntener U, Umana P. Modulation of therapeutic antibody effector functions by glycosylation engineering: influence of Golgi enzyme localization domain and coexpression of heterologous beta1, 4-N-acetylglucosaminyltransferase III and Golgi alpha-mannosidase II. Biotechnol Bioeng 2006;93:851-61.
33. Schraml M, von PL. Temperature-dependent antibody kinetics as a tool in antibody lead selection. Methods Mol Biol 2012;901:183-94.
34. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. J Appl Crystallogr 2007; 40:658-74.
35. Cho HS, Leahy DJ. Structure of the extracellular region ofHER3 reveals an interdomain tether. Science 2002;297:1330-3.
36. McLellan JS, Pancera M, Carrico C, Gorman J, Julien JP, Khayat R, et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 2011;480:336-43.
37. Schaefer G, Haber L, Crocker LM, Shia S, Shao L, Dowbenko D, 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.
38. Brunger AT. Version 1.2 of the crystallography and NMR system. Nat Protoc 2007;2:2728-33.
39. Krissinel E, Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol 2007;372:774-97.
40. Gerdes CA, Nicolini V, Herter S, van Puijenbroek E, Lang S, Roemmele M, et al. GA201 (RG7160): a novel, humanised, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab. Clin Cancer Res 2013;19: 1126-38.
41. Amin DN, Campbell MR, Moasser MM. The role of HER3, the unpretentious member of the HER family, in cancer biology and cancer therapeutics. Semin Cell Dev Biol 2010;21:944-50.
42. Pinkas-Kramarski R, Soussan L, Waterman H, Levkowitz G, Alroy I, Klapper L, et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 1996;15:2452-67.
43. Jura N, Shan Y, Cao X, Shaw DE, Kuriyan J. Structural analysis of the catalytically inactive kinase domain of the human EGF receptor Proc Natl Acad Sci U S A 2009;106:21608-13.
44. Wedemayer GJ, Patten PA, Wang LH, Schultz PG, Stevens RC. Structural insights into the evolution of an antibody combining site. Science 1997;276:1665-9.
45. Kani K, Park E, Landgraf R. The extracellular domains of ErbB3 retain high ligand binding affinity at endosome pH and in the locked conformation. Biochemistry 2005;44:15842-57.
46. Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim JH, et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell 2002;110:775-87.
47. van der Horst EH, Murgia M, Treder M, Ullrich A. Anti-HER-3 MAbs inhibit HER-3-mediated signaling in breast cancer cell lines resistant to anti-HER-2 antibodies. Int J Cancer 2005;115:519-27.
48. Schoeberl B, Faber AC, Li D, Liang MC, Crosby K, Onsum M, et al. An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer Res 2010;70:2485-94.
49. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, et al. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol 2007;25:3712-8.