title: A human IgG-like bispecific antibody co-targeting epidermal growth factor receptor and the vascular endothelial growth factor receptor 2 for enhanced antitumor activity.
abstract: Both Epidermal Growth Factor Receptor (EGFR) and the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) play critical roles in tumorigenesis. We hypothesized co-targeting EGFR and VEGFR2 using a bispecific antibody might have significant therapeutic potential. Here,we designed and produced a human IgG-like bispecific antibody (Bi-Ab) based on the variable regions of cetuximab (an anti-EGFR antibody) and mAb-04 (an anti-VEGFR2 antibody developed in our lab) . The Bi-Ab was found to inhibit the proliferation, survival and invasion of cancer cells via ablating phosphorylation of receptor and downstream signaling. In vivo efficacy was demonstrated against established HT-29 and SKOV-3 xenografts grown in nude mice. Studies revealed our Bi-Ab was able to restrain xenografted tumor growth and prolong survival of mice through inhibiting cell proliferation,promoting apoptosis and anti-angiogenesis. In contrast to cetuximab or mAb-04 alone, our Bi-Ab exhibits enhanced antitumor activity and has equal or slightly superior activity to their combination (Combi). It shows promise as a therapeutic agent, especially for use against tumors EGFR and/or VEGFR2 over-expressing malignancies.
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.|b Department of Biotechnology and Environmental Science , Changsha University , Changsha , China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Desmond Omane
authors.initials: DO
authors.lastname: Acheampong
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Menghuai
authors.initials: M
authors.lastname: Xu
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Mengqi
authors.initials: M
authors.lastname: Yang
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Luo
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D061067:Antibodies, Monoclonal, Humanized; C512478:EGFR protein, human; D066246:ErbB Receptors; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Bispecific antibody; EGFR; VEGFR2; cancer therapy; co-targeting