Sym004, a novel anti-Egfr antibody mixture, augments radiation response in human lung and head and neck cancers

Molecular Cancer Therapeutics

Volumn 12, Issue 12, 2013, Pages 2772-2781

  Huang, Shyhmin ^a   Peet, Chimera R ^a   Saker, Jarob ^a   Li, Chunrong ^a   Armstrong, Eric A ^a   Kragh, Michael ^b   Pedersen, Mikkel W ^b   Harari, Paul M ^a  

^a UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^b Symphogen AS   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

BRCA1 PROTEIN; DNAPK PROTEIN; DOUBLE STRANDED DNA; FUTUXIMAB; HISTONE GAMMA H2AX; HISTONE H2AX; MESSENGER RNA; NIBRIN; RAD50 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER GROWTH; CANCER RADIOTHERAPY; CANCER SURVIVAL; CELL ASSAY; CELL CYCLE ARREST; CELL DEATH; CELL PROLIFERATION; CLONOGENESIS; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; DOUBLE STRANDED DNA BREAK; HEAD AND NECK CANCER; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; LUNG CANCER; LUNG SMALL CELL CANCER; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIATION RESPONSE; TREATMENT OUTCOME; TUMOR XENOGRAFT;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DNA DAMAGE; DNA REPAIR; HEAD AND NECK NEOPLASMS; HUMANS; LUNG NEOPLASMS; MICE; PROTEOLYSIS; RADIATION TOLERANCE; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84890490369     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-13-0587     Document Type: Article

References (32)

1. Masui H, Kawamoto T, Sato JD, Wolf B, Sato G,Mendelsohn J. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res 1984;44:1002-7
2. Wheeler DL, Dunn EF, Harari PM. Understanding resistance to egfr inhibitors[mdash]impact on future treatment strategies. Nat Rev Clin Oncol 2010;7:493-507
3. Huang S, Bock JM, Harari PM. Epidermal growth factor receptor blockade with c225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 1999;59:1935-40
4. Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, et al. In vivo enhancement of tumor radioresponse by c225 antiepidermal growth factor receptor antibody. Clin Cancer Res 2000;6:701-8
5. Kruser TJ, Armstrong EA, Ghia AJ, Huang S, Wheeler DL, Radinsky R, et al. Augmentation of radiation response by panitumumab in models of upper aerodigestive tract cancer. Int J Radiat Oncol Biol Phys 2008;72:534-42
6. Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol 2006;33:369-85
7. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78
8. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11:21-28
9. Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010;28:357-60
10. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, et al. Genotypic and histological evolution of lung cancers acquiring resistance to egfr inhibitors. Sci Transl Med 2011;3:75-26
11. Friedman LM, Rinon A, Schechter B, Lyass L, Lavi S, Bacus SS, et al. Synergistic down-regulation of receptor tyrosine kinases by combinations of mabs: implications for cancer immunotherapy. Proc Natl Acad Sci U S A 2005;102:1915-20
12. Ben-Kasus T, Schechter B, Lavi S, Yarden Y, Sela M. Persistent elimination of erbb-2/her2-overexpressing tumors using combinations of monoclonal antibodies: Relevance of receptor endocytosis. Proc Natl Acad Sci U S A 2009;106:3294-99
13. Spangler JB, Neil JR, Abramovitch S, Yarden Y, White FM, Lauffenburger DA, et al. Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling. Proc Natl Acad Sci U S A 2010;107:13252-57
14. Dechant M, Weisner W, Berger S, Peipp M, Beyer T, Schneider-Merck T, et al. Complement-dependent tumor cell lysis triggered by combinations of epidermal growth factor receptor antibodies. Cancer Res 2008;68:4998-5003
15. Koefoed K, Steinaa L, Soderberg JN, Kjaer I, Jacobsen HJ, Meijer PJ, et al. Rational identification of an optimal antibody mixture for targeting the epidermal growth factor receptor. MAbs 2011;3:584-95
16. Pedersen MW, Jacobsen HJ, Koefoed K, Hey A, Pyke C, Haurum JS, et al. Sym004: A novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer efficacy. Cancer Res 2010;70:588-97
17. Benavente S, Huang S, Armstrong EA, Chi A, Hsu K-T, Wheeler DL, et al. Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells. Clin Cancer Res 2009;15:1585-92
18. Mandic R, Rodgarkia-Dara CJ, Zhu L, Folz BJ, Bette M, Weihe E, et al. Treatment of hnscc cell lines with the egfr-specific inhibitor cetuximab (erbituxæ) results in paradox phosphorylation of tyrosine 1173 in the receptor. FEBS Lett 2006;580:4793-800
19. Schmidt-Ullrich RK, Contessa JN, Lammering G, Amorino G, Lin PS. Erbb receptor tyrosine kinases and cellular radiation responses. Oncogene 2003;22:5855-65
20. Huang S-M, Harari PM. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: Inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res 2000;6:2166-74
21. Dittmann K, Mayer C, Rodemann H. Inhibition of radiation-induced egfr nuclear import by c225 (cetuximab) suppresses DNA-pk activity. Radiother Oncol 2005;76:157-61
22. Ryu S-H, Lee S-W, Yang Y-J, Song SY, Kim JH, Choi EK, et al. Intracytoplasmic epidermal growth factor receptor shows poor response to the cetuximab antitumor effect in irradiated non-small cell lung cancer cell lines. Lung Cancer 2012;77:482-87
23. Psyrri A, Egleston B, Pectasides E, Weinberger P, Yu Z, Kowalski D, et al. Correlates and determinants of nuclear epidermal growth factor receptor content in an oropharyngeal cancer tissue microarray. Cancer Epidemiol Biomarkers Prev 2008;17:1486-92
24. Chinnaiyan P, Huang S, Vallabhaneni G, Armstrong E, Varambally S, Tomlins SA, et al. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res 2005;65:3328-35
25. Wang Y-N, Yamaguchi H, Huo L, Du Y, Lee H-J, Lee H-H, et al. The translocon sec61ϲ localized in the inner nuclear membrane transports membrane-embedded egf receptor to the nucleus. J Biol Chem 2010;285:38720-29
26. Lo HW, Ali-Seyed M, Wu Y, Bartholomeusz G, Hsu SC, Hung MC. Nuclear-cytoplasmic transport of egfr involves receptor endocytosis, importin beta1 and crm1. J Cell Biochem 2006;98:1570-83
27. Liao H-J, Carpenter G. Cetuximab/c225-induced intracellular trafficking of epidermal growth factor receptor. Cancer Res 2009;69: 6179-83
28. Li C, Iida M, Dunn EF, Wheeler DL. Dasatinib blocks cetuximab-and radiation-induced nuclear translocation of the epidermal growth factor receptor in head and neck squamous cell carcinoma. Radiother Oncol 2010;97:330-37
29. Yu Y-L, Chou R-H, Wu C-H, Wang Y-N, Chang W-J, Tseng Y-J, et al. Nuclear egfr suppresses ribonuclease activity of polynucleotide phosphorylase through DNAPK-mediated phosphorylation at serine 776. J Biol Chem 2012;287:31015-26
30. Skartved NJØ, Jacobsen HJ, Pedersen MW, Jensen PF, Sen JW, Jørgensen TK, et al. Preclinical pharmacokinetics and safety of sym004: A synergistic antibody mixture directed against epidermal growth factor receptor. Clin Cancer Res 2011;17:5962-72
31. Machiels J-PH, Specenier PM, Krauss J, Dietz A, Kaminsky M-C, Lalami Y, et al. Sym004, a novel strategy to target egfr with an antibody mixture, in patients with advanced scchn progressing after anti-egfr monoclonal antibody: A proof of concept study. J Clin Oncol 31, 2013 (suppl; abstr 6002)
32. Dienstmann R, Tabernero J, Cutsem EV, Cervantes-Ruiperez A, Keranen SR, Viñuales MB, et al. Proof-of-concept study of sym004, an anti-egfr monoclonal antibody (mab) mixture, in patients (pts) with anti-egfr mab-refractory kras wild-type (wt) metastatic colorectal cancer (mcrc). J Clin Oncol 31, 2013 (suppl; abstr 3551)