Pan-HER—An antibody mixture targeting EGFR, HER2 and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers

International Journal of Cancer

Volumn 139, Issue 9, 2016, Pages 2095-2105

  Ellebæk, Sofie ^a   Brix, Susanne ^b   Grandal, Michael ^a   Lantto, Johan ^a   Horak, Ivan D ^a   Kragh, Michael ^a   Poulsen, Thomas Tuxen ^a  

^a Symphogen AS   (Denmark)

^b TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

antibodies; dimerization; EGFR; HER family

Indexed keywords

CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; HETERODIMER; HOMODIMER; PERTUZUMAB; TRASTUZUMAB;

ARTICLE; CANCER CELL LINE; CELL PROLIFERATION; CONTROLLED STUDY; DIMERIZATION; DOWN REGULATION; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN TARGETING; SIGNAL TRANSDUCTION;

EID: 85028269298     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.30242     Document Type: Article

References (48)

1. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010;141:1117–34.
2. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001;2:127–37.
3. Roskoski R. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res 2014;79:34–74.
4. Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006;366:2–16.
5. Yamaguchi H, Chang SS, Hsu JL, et al. Signaling cross-talk in the resistance to HER family receptor targeted therapy. Oncogene 2014;33:1073–81.
6. Kruser TJ, Wheeler DL. Mechanisms of resistance to HER family targeting antibodies. Exp Cell Res 2010;316:1083–100.
7. Arteaga CL. Epidermal growth factor receptor dependence in human tumors: more than just expression? Oncologist 2002;7:31–9.
8. Tao RH, Maruyama IN. All EGF(ErbB) receptors have preformed homo- and heterodimeric structures in living cells. J Cell Sci 2008;121:3207–17.
9. Liu P, Sudhaharan T, Koh RML, et al. Investigation of the dimerization of proteins from the epidermal growth factor receptor family by single wavelength fluorescence cross-correlation spectroscopy. Biophys J 2007;93:684–98.
10. Moriki T, Maruyama H, Maruyama IN. Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain. J Mol Biol 2001;311:1011–26.
11. Habib AA, Chun SJ, Neel BG, et al. Increased expression of epidermal growth factor receptor induces sequestration of extracellular signal-related kinases and selective attenuation of specific epidermal growth factor-mediated signal transduction pathways. Mol Cancer Res 2003;1:219–33.
12. Knuefermann C, Lu Y, Liu B, et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene 2003;22:3205–12.
13. Smolen GA, Sordella R, Muir B, et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc Natl Acad Sci USA 2006;103:2316–21.
14. Burgess AW, Cho H, Eigenbrot C, et al. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell 2003;12:541–52.
15. Graus-Porta D, Beerli RR, Daly JM, et al. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 1997;16:1647–55.
16. Citri A, Skaria KB, Yarden Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res 2003;284:54–65.
17. Kim HH, Sierke SL, Koland JG. Epidermal growth factor-dependent association of phosphatidylinositol 3-kinase with the erbB3 gene product. J Biol Chem 1994;269:24747–55.
18. Roepstorff K, Grøvdal L, Grandal M., et al. Endocytic down-regulation of ErbB receptors: mechanisms and relevance in cancer. Histochem Cell Biol 2008;129:563–78.
19. Baulida J, Carpenter G. Heregulin degradation in the absence of rapid receptor-mediated internalization. Exp Cell Res 1997;232:167–72.
20. Baulida J, Kraus MH, Alimandi M, et al. All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol Chem 1996;271:5251–7.
21. Wang Z, Zhang L, Yeung TK, et al. Endocytosis deficiency of epidermal growth factor (EGF) receptor-ErbB2 heterodimers in response to EGF stimulation. Mol Biol Cell 1999;10:1621–36.
22. Lenferink AEG, Pinkas-Kramarski R, van de Poll MLM, et al. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. Eur Mol Biol Org J 1998;17:3385–97.
23. Hendriks BS, Opresko LK, Wiley HS, et al. Coregulation of epidermal growth factor receptor/human epidermal growth factor receptor 2 (HER2) levels and locations: quantitative analysis of HER2 overexpression effects. Cancer Res 2003;63:1130–7.
24. Sliwkowski MX, Mellman I. Antibody therapeutics in cancer. Science 2013;341:1192–8.
25. U.S. National Institues of Health, MM-121 registrated trials. Available at: http://www.clinicaltrials.gov/ct2/results?term=MM-121.
26. Schoeberl B, Faber AC, Li D, et al. An ErbB3 antibody, MM-121, is active in cancers with ligand dependent activation. Cancer Res 2011;70:2485–2494.
27. Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene 2008;27:3944–56.
28. Ritter CA, Perez-Torres M, Rinehart C, et al. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res 2007;13:4909–19.
29. Dua R, Zhang J, Nhonthachit P, et al. EGFR over-expression and activation in high HER2, ER negative breast cancer cell line induces trastuzumab resistance. Breast Cancer Res Treat 2010;122:685–97.
30. Pedersen MW, Jacobsen HJ, Koefoed K, et al. Sym004: a novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer efficacy. Cancer Res 2010;70:588–97.
31. Friedman LM, Rinon A, Schechter B, et al. Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy. Proc Natl Acad Sci USA 2005;102:1915–20.
32. Yamashita-Kashima Y, Iijima S, Yorozu K, et al. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res 2011;17:5060–70.
33. Nahta R, Hung MC, Esteva FJ. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res 2004;64:2343–2346.
34. Pedersen MW, Jacobsen HJ, Koefoed K, et al. Targeting three distinct HER2 domains with a recombinant antibody mixture overcomes trastuzumab resistance. Mol Cancer Ther 2015;14:669–80.
35. Quesnelle KM, Grandis JR. Dual kinase inhibition of EGFR and HER2 overcomes resistance to cetuximab in a novel in vivo model of acquired cetuximab resistance. Clin Cancer Res 2011;17:5935–44.
36. Pollock N, Wang L, Wallweber G, et al. Increased expression of HER2, HER3, and HER2:HER3 heterodimers in HPV-positive HNSCC using a novel proximity-based assay: Implications for targeted therapies. Clin Cancer Res 2015;2:1–36.
37. Thomas G, Chardès T, Gaborit N, et al. HER3 as biomarker and therapeutic target in pancreatic cancer: new insights in pertuzumab therapy in preclinical models. Oncotarget 2014;5:7138–48.
38. Jacobsen HJ, Poulsen TT, Dahlman A, et al. Pan-HER, an antibody mixture simultaneously targeting EGFR, HER2 and HER3 effectively overcomes tumor heterogeneity and plasticity. Clin Cancer Res 2015;21:4110–22.
39. Koefoed K, Steinaa L, Søderberg JN, et al. Rational identification of an optimal antibody mixture for targeting the epidermal growth factor receptor. mAbs 2011;3:584–95.
40. Pedersen MW, Jacobsen H, Koefoed K. Anti-HER3 antibodies and compositions. U.S. Patent Application No. WO2012/059858 A1, 2012.
41. Larbouret C, Gaborit N, Robert B, et al. In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption. Neoplasia 2012;14:121–30.
42. Zheng L, Tan W, Zhang J, et al. Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer by effective inhibition of EGFR/ErbB2 heterodimerization and signaling. Cancer Immunol Immunother 2014;63:581–6.
43. Li C, Iida M, Dunn EF, et al. Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene 2009;28:3801–13.
44. Agus DB, Akita RW, Fox WD, et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2002;2:127–37.
45. Choi BK, Fan X, Deng H, et al. ERBB3 (HER3) is a key sensor in the regulation of ERBB-mediated signaling in both low and high ERBB2 (HER2) expressing cancer cells. Cancer Med 2012;1:28–38.
46. Hughes JB, Berger C, Rødland MS, et al. Pertuzumab increases epidermal growth factor receptor down-regulation by counteracting epidermal growth factor receptor-ErbB2 heterodimerization. Mol Cancer Ther 2009;8:1885–92.
47. DeFazio-Eli L, Strommen K, Dao-Pick T, et al. Quantitative assays for the measurement of HER1-HER2 heterodimerization and phosphorylation in cell lines and breast tumors: applications for diagnostics and targeted drug mechanism of action. Breast Cancer Res 2011;13:1–18.
48. Li S, Schmitz KR, Jeffrey PD, et al. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005;7:301–11.