A monoclonal antibody targeting the dimer interface of epidermal growth factor receptor (EGFR).
Epidermal growth factor receptor (EGFR) is an attractive target for the treatment of epithelial cancers. However, EGFR antagonists have low clinical response rates and frequently induce resistance mainly caused by the hypermutation of the extracellular and intracellular domains and the heterodimerization of EGFR. Dimerization plays a key role in the activation of the EGFR family of receptors. Thus, targeting the highly conserved dimer interface of EGFR maybe an attractive strategy for improving the clinical response of anti-EGFR therapies. In this work, we report a monoclonal antibody (mAb) called Antidimer 5G9 that targets the β-hairpin within the dimer interface of EGFR, which is 100% homologous with mouse EGFR. Antidimer 5G9 belongs to the isotype IgG1 and bound with an affinity constant of 1.837×109L/mol. Just as designed and expected, Antidimer 5G9 could recognize and bind to human EGFRs or mouse EGFRs on the surface of human breast cancer cells of the MDA-MB-231 cell line or mouse Lewis lung cancer cells (LLC), effectively inhibiting growth and inducing apoptosis in the targeted cells. This work lays the foundation for further studies investigating the feasibility of this strategy for targeting the dimer interface of EGFR and developing novel anti-EGFR drugs.
Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Tujing
T
Guo
Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Lin
L
Zhao
Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Yawen
Y
Zhang
Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Guoqiang
G
Liu
Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Yuanhang
Y
Yao
Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: 1002304772@qq.com.
Huangjin
H
Li
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D066246:ErbB Receptors
Anti-cancer; Dimer interface; Dimerization; EGFR; Monoclonal antibody