Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 43, 2015, Pages 13225-13230

  Lee, Sangwon ^a   Greenlee, Etienne B ^a   Amick, Joseph R ^a   Ligon, Gwenda F ^b   Lillquist, Jay S ^b   Natoli, Edward J ^b   Hadari, Yaron ^b   Alvarado, Diego ^b   Schlessinger, Joseph ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Kolltan Pharmaceuticals   (United States)

Author keywords

Cancer; Cell signaling; Crystal structure; Surface receptor; Therapeutic antibodies

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; EPITOPE; IMMUNOGLOBULIN F(AB) FRAGMENT; KTN 3379; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; ERBB3 PROTEIN, HUMAN;

ALLOSTERISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BINDING AFFINITY; BINDING KINETICS; BREAST CANCER CELL LINE; CANCER PATIENT; CRYSTAL STRUCTURE; HUMAN; HUMAN CELL; LIGAND BINDING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CRYSTALLOGRAPHY; ENZYME LINKED IMMUNOSORBENT ASSAY; EXTRACELLULAR SPACE; FLOW CYTOMETRY; MOLECULAR MODEL; PROTEIN TERTIARY STRUCTURE;

ANTIBODIES, MONOCLONAL; CRYSTALLOGRAPHY; ENZYME-LINKED IMMUNOSORBENT ASSAY; EXTRACELLULAR SPACE; FLOW CYTOMETRY; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; RECEPTOR, ERBB-3;

EID: 84945544237     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1518361112     Document Type: Article

References (36)

1. Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117-1134.
2. Arteaga CL, Engelman JA (2014) ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25(3):282-303.
3. Arteaga CL (2003) ErbB-targeted therapeutic approaches in human cancer. Exp Cell Res 284(1):122-130.
4. Falls DL (2003) Neuregulins: Functions, forms, and signaling strategies. Exp Cell Res 284(1):14-30.
5. Shi F, Telesco SE, Liu Y, Radhakrishnan R, Lemmon MA (2010) ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc Natl Acad Sci USA 107(17):7692-7697.
6. Jura N, Shan Y, Cao X, Shaw DE, Kuriyan J (2009) Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3. Proc Natl Acad Sci USA 106(51): 21608-21613.
7. Funayama T, et al. (1998) Overexpression of c-erbB-3 in various stages of human squamous cell carcinomas. Oncology 55(2):161-167.
8. Lee-Hoeflich ST, et al. (2008) A central role for HER3 in HER2-amplified breast cancer: Implications for targeted therapy. Cancer Res 68(14):5878-5887.
9. Ocana A, et al. (2013) HER3 overexpression and survival in solid tumors: A metaanalysis. J Natl Cancer Inst 105(4):266-273.
10. Chakrabarty A, Sánchez V, Kuba MG, Rinehart C, Arteaga CL (2012) Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci USA 109(8):2718-2723.
11. Burgess AW, et al. (2003) An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell 12(3):541-552.
12. Dawson JP, et al. (2005) Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface. Mol Cell Biol 25(17):7734-7742.
13. Dawson JP, Bu Z, Lemmon MA (2007) Ligand-induced structural transitions in ErbB receptor extracellular domains. Structure 15(8):942-954.
14. Schoeberl B, et al. (2010) An ErbB3 antibody, MM-121, is active in cancers with liganddependent activation. Cancer Res 70(6):2485-2494.
15. Mirschberger C, et al. (2013) RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation. Cancer Res 73(16): 5183-5194.
16. Schaefer G, et al. (2011) A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell 20(4):472-486.
17. Di Fiore PP, et al. (1987) erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science 237(4811):178-182.
18. Slamon DJ, et al. (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(4905):707-712.
19. Dall'Acqua WF, Kiener PA, Wu H (2006) Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 281(33): 23514-23524.
20. Garner AP, et al. (2013) An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin. Cancer Res 73(19):6024-6035.
21. Sergina NV, et al. (2007) Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 445(7126):437-441.
22. Abel EV, et al. (2013) Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J Clin Invest 123(5):2155-2168.
23. Cho HS, Leahy DJ (2002) Structure of the extracellular region of HER3 reveals an interdomain tether. Science 297(5585):1330-1333.
24. Lawrence MC, Colman PM (1993) Shape complementarity at protein/protein interfaces. J Mol Biol 234(4):946-950.
25. Li S, et al. (2005) Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 7(4):301-311.
26. Liu P, et al. (2012) A single ligand is sufficient to activate EGFR dimers. Proc Natl Acad Sci USA 109(27):10861-10866.
27. Lu C, et al. (2010) Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor. Mol Cell Biol 30(22): 5432-5443.
28. Bostrom J, et al. (2009) Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323(5921):1610-1614.
29. Arkhipov A, Shan Y, Kim ET, Dror RO, Shaw DE (2013) Her2 activation mechanism reflects evolutionary preservation of asymmetric ectodomain dimers in the human EGFR family. eLife 2:e00708.
30. Alvarado D, Klein DE, Lemmon MA (2009) ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor. Nature 461(7261):287-291.
31. Alvarado D, Klein DE, Lemmon MA (2010) Structural basis for negative cooperativity in growth factor binding to an EGF receptor. Cell 142(4):568-579.
32. Heras B, Martin JL (2005) Post-crystallization treatments for improving diffraction quality of protein crystals. Acta Crystallogr D Biol Crystallogr 61(Pt 9):1173-1180.
33. Kabsch W (2010) Xds. Acta Crystallogr D Biol Crystallogr 66(Pt 2):125-132.
34. Adams PD, et al. (2010) PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66(Pt 2):213-221.
35. Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66(Pt 4):486-501.
36. Laskowski RA (2007) Enhancing the functional annotation of PDB structures in PDBsum using key figures extracted from the literature. Bioinformatics 23(14): 1824-1827.