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1、EGFR and VEGFR2 overexpressing tumors. V 2016 American Institute of Chemical Engi-A Novel Bispecific Diabody Targeting both Vascular Endothelial GrowthFactor Receptor 2 and Epidermal Growth Factor Receptor for EnhancedAntitumor ActivityMenghuai Xu, Haizhen Jin, Zhiguo
2、Chen, Wei Xie, Youfu Wang, Yang Wang, Min Wang, andJuan ZhangState Key Laboratory of Natural Medicines (China Pharmaceutical University), School of Life Science & Technology, ChinaPharmaceutical University, Nanjing 210009, People’s Republic of ChinaDesmond Omane Achea
3、mpongState Key Laboratory of Natural Medicines (China Pharmaceutical University), School of Life Science & Technology, ChinaPharmaceutical University, Nanjing 210009, People’s Republic of ChinaDept. of Biomedical Sciences, School of Allied Health Sciences, University
4、of Cape Coast, Cape Coast, GhanaDOI 10.1002/btpr.2231Published online February 13, 2016 in Wiley Online Library (wileyonlinelibrary.com)Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor2 (VEGFR2) are receptor tyrosine kinases know
5、n to play critical roles in the developmentand progression of tumors. Based on the cross-talk between EGFR and VEGFR2 signalpathways, we designed and produced a bispecific diabody (bDAb) targeting both EGFR andVEGFR2 simultaneously. The bispecific molecule (EK-02) demon
6、strated that it could bind toHUVEC (VEGFR2 high-expressing) and A431 (EGFR overexpressing) cells. Additionally,similar to the parental antibodies, it was able to inhibit proliferation and migration, andinduced apoptosis in these cells (HUVECs and A431), demonstrating
7、that it had retained thefunctional properties of its parental antibodies. Furthermore, the efficacy of EK-02 was eval-uated using the human colon adenocarcinoma cell line HT29 (VEGFR2 and EGFR coex-pressing). In vitro assay showed that EK-02 could bind to HT29 cells, r
8、estrain cell growthand migration, and induce apoptosis with enhanced efficacy compared to both parental anti-bodies. Further,
