Characterization of a new dual-targeting fully human antibody with potent antitumor activity against nasopharyngeal carcinoma
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Shenzhi Xie
Abstract
Despite the effectiveness of the anti-EGFR chimeric antibody (mAb), cetuximab, in treating nasopharyngeal carcinoma (NPC), its efficacy remains variable and often modest. In this study, a full human dual targeted anti-EGFR/HER3 antibody, CA1182, was generated from phage display library. CA1182 was as effective as cetuximab or trastuzumab in inhabiting phosphorylation of EGFR or HER2, but it exhibited as much more potent than cetuximab or trastuzumab. Moreover, our studies showed that CA1182 was significantly more effective than cetuximab in prolonging the survival of severe combined immune deficient mice bearing human NPC, suggesting that it might be a promising therapeutic agent for NPC.
References
Agus, D.B., Akita, R.W., Fox, W.D., Lewis, G.D., Higgins, B., Pisacane, P.I., Lofgren, J.A., Tindell, C., Evans, D.P., Maiese, K., et al. (2002). Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2, 127–137.10.1016/S1535-6108(02)00097-1Search in Google Scholar
Franklin, M.C., Carey, K.D., Vajdos, F.F., Leahy, D.J., de Vos, A.M., and Sliwkowski, M.X. (2004). Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5, 317–328.10.1016/S1535-6108(04)00083-2Search in Google Scholar
Fu, W., Wang, Y., Zhang, Y., Xiong, L., Takeda, H., Ding, L., Xu, Q., He, L., Tan, W., Bethune, A.N., et al. (2014). Insights into HER2 signaling from step-by-step optimization of anti-HER2 antibodies. Paper presented at the mAbs, 6(4), 978–990.10.4161/mabs.28786Search in Google Scholar
Grothey, A. (2010). EGFR antibodies in colorectal cancer: where do they belong? J. Clin. Oncol. 28, 4668–4670.10.1200/JCO.2010.29.3407Search in Google Scholar
Hu, S., Liang, S., Guo, H., Zhang, D., Li, H., Wang, X., Yang, W., Qian, W., Hou, S., Wang, H., et al. (2013). Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor α-associated diseases from a molecular view. J. Biol. Chem. 288, 27059–27067.10.1074/jbc.M113.491530Search in Google Scholar
Jia, W.-H., Huang, Q.-H., Liao, J., Ye, W., Shugart, Y., Liu, Q., Chen, L.Z., Li, Y.H., Lin, X., Wen, F.L., et al. (2006). Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983–2002) in Sihui and Cangwu counties in southern China. BMC Cancer 6, 178.10.1186/1471-2407-6-178Search in Google Scholar
Lanier, A.P., Bornkamm, G.W., Henle, W., Henle, G., Bender, T.R., Talbot, M.L., and Dohan, P.H. (1981). Association of Epstein-Barr virus with nasopharyngeal carcinoma in alaskan native patients: serum antibodies and tissue EBNA and DNA. Int. J. Cancer 28, 301–305.10.1002/ijc.2910280308Search in Google Scholar
Liu, T. (1999). Issues in the management of nasopharyngeal carcinoma. Crit. Rev. Oncol. Hematol. 31, 55–69.10.1016/S1040-8428(99)00003-7Search in Google Scholar
Lynch, T.J., Bell, D.W., Sordella, R., Gurubhagavatula, S., Okimoto, R.A., Brannigan, B.W., Harris, P.L., Haserlat, S.M., Supko, J.G., Haluska, F.G., et al. (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139.10.1056/NEJMoa040938Search in Google Scholar PubMed
Mimi, C.Y., Ho, J.H., Lai, S.-H., and Henderson, B.E. (1986). Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong. Cancer Res. 46, 956–961.Search in Google Scholar
Muthuswamy, S.K., Gilman, M., and Brugge, J.S. (1999). Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol. Cell. Biol. 19, 6845–6857.10.1128/MCB.19.10.6845Search in Google Scholar PubMed PubMed Central
Niedobitek, G. (2000). Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Mol. Pathol. 53, 248–254.10.1136/mp.53.5.248Search in Google Scholar
Niedobitek, G., Hansmann, M.L., Herbst, H., Young, L.S., Dienemann, D., Hartmann, C.A., Finn, T., Pitteroff, S., Welt, A., Anagnostopoulos, I., et al. (1991). Epstein-Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J. Pathol. 165, 17–24.10.1002/path.1711650105Search in Google Scholar
Old, L., Boyse, E., Oettgen, H., De Harven, E., Geering, G., Williamson, B., and Clifford, P. (1966). Precipitating antibody in human serum to an antigen present in cultured Burkitt’s lymphoma cells. Proc. Natl. Acad. Sci. USA 56, 1699.10.1073/pnas.56.6.1699Search in Google Scholar
Parkin, D.M., Bray, F., Ferlay, J., and Pisani, P. (2005). Global cancer statistics, 2002. CA Cancer J. Clin. 55, 74–108.10.3322/canjclin.55.2.74Search in Google Scholar
Schaefer, A., Magocsi, M., and Marquardt, H. (1997). Signalling mechanisms in erythropoiesis: the enigmatic role of calcium. Cell Signal 9, 483–495.10.1016/S0898-6568(97)00094-6Search in Google Scholar
©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Reviews
- Ras activation revisited: role of GEF and GAP systems
- When core competence is not enough: functional interplay of the DEAD-box helicase core with ancillary domains and auxiliary factors in RNA binding and unwinding
- Cathepsin S: therapeutic, diagnostic, and prognostic potential
- Minireview
- Overview of the roles of Sox2 in stem cell and development
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Transcriptional and translational mechanisms contribute to regulate the expression of Discs Large 1 protein during different biological processes
- Membranes, Lipids, Glycobiology
- Rapid transfer of overexpressed integral membrane protein from the host membrane into soluble lipid nanodiscs without previous purification
- Molecular Medicine
- Characterization of a new dual-targeting fully human antibody with potent antitumor activity against nasopharyngeal carcinoma
- Cell Biology and Signaling
- Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres
- SIRT2 suppresses non-small cell lung cancer growth by targeting JMJD2A
- Troglitazone suppresses glutamine metabolism through a PPAR-independent mechanism
Articles in the same Issue
- Frontmatter
- Reviews
- Ras activation revisited: role of GEF and GAP systems
- When core competence is not enough: functional interplay of the DEAD-box helicase core with ancillary domains and auxiliary factors in RNA binding and unwinding
- Cathepsin S: therapeutic, diagnostic, and prognostic potential
- Minireview
- Overview of the roles of Sox2 in stem cell and development
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Transcriptional and translational mechanisms contribute to regulate the expression of Discs Large 1 protein during different biological processes
- Membranes, Lipids, Glycobiology
- Rapid transfer of overexpressed integral membrane protein from the host membrane into soluble lipid nanodiscs without previous purification
- Molecular Medicine
- Characterization of a new dual-targeting fully human antibody with potent antitumor activity against nasopharyngeal carcinoma
- Cell Biology and Signaling
- Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres
- SIRT2 suppresses non-small cell lung cancer growth by targeting JMJD2A
- Troglitazone suppresses glutamine metabolism through a PPAR-independent mechanism
