文献类型：期刊文献

英文题名：Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody

作者：Liu, Xianglei[1,2];Zhelev, Doncho[1];Adams, Cynthia[1];Chen, Chuan[1];Mellors, John W.[1,3];Dimitrov, Dimiter S.[1,3]

机构：[1]Univ Pittsburgh Sch Med, Ctr Antibody Therapeut, Dept Med, Div Infect Dis, S843 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA;[2]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Abound Bio, 1401 Forbes Ave, Pittsburgh, PA 15219 USA

年份：2021

卷号：14

期号：12

外文期刊名：TRANSLATIONAL ONCOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000724825900007)】；

基金：We thank the members of the Center for Antibody Therapeutics: WeiLi, Zehua Sun, Xiaojie Chu, Du-San Baek, and Yae-Jin Kim for helpful discussions. This work was supported by the UPMC.

语种：英文

外文关键词：Fully human antibody; CD276 (B7-H3); V1/V2 domain; Bispecific T cell engager (BiTE)

摘要：The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (10(11)) phage-displayed single-chain variable fragment (scF(v)) library, a fully human antibody, B11, which bound with high avidity (K-D=0.4 nM) to CD276. B11 specifically bound to the V1/V2 domain of CD276 and competed with the antibody 8H9 (Omburtamab). It was used to design an IgG-format bispecific T cell engager B11-BiTE, which was more effective than 8H9-BiTE in 14 different cancer cell lines. B11-BiTE also exhibited strong ADCC/ADCP. Therefore, the fully human B11-BiTE is a promising candidate for treatment of tumors expressing CD276.