a novel bispecific diabody targeting both vascular endothelial growth factor receptor 2 and epidermal growth factor receptor for

a novel bispecific diabody targeting both vascular endothelial growth factor receptor 2 and epidermal growth factor receptor for

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時間：2018-07-20

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1、EGFR?and?VEGFR2?overexpressing?tumors.?V?2016?American?Institute?of?Chemical?Engi-A?Novel?Bispeci?c?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?bispeci?c?diabody?(bDAb)?targeting?both?EGFR?andVEGFR2?simultaneously.?The?bispeci?c?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?ef?cacy?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?ef?cacy?compared?to?both?parental?anti-bodies.?Further,

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