A Human IgG-like Bispecific Antibody Co-targeting Epidermal Growth Factor Receptor and the Vascular Endothelial Growth Factor Receptor 2 for Enhanced Antitumor Activity.

A Human IgG-like Bispecific Antibody Co-targeting Epidermal Growth Factor Receptor and the Vascular Endothelial Growth Factor Receptor 2 for Enhanced Antitumor Activity.

Cancer Biol Ther. 2015 Dec 15;:0

Authors: Chen Z, Xie W, Acheampong DO, Xu M, He H, Yang M, Li C, Luo C, Wang M, Zhang J

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.

PMID: 26671532 [PubMed - as supplied by publisher]

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