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

基于新型全人抗体的双特异性 T 细胞接合器可有效杀死表达 CD276 (B7-H3) 的细胞

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作者:Xianglei Liu, Doncho Zhelev, Cynthia Adams, Chuan Chen, John W Mellors, Dimiter S Dimitrov

Abstract

The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (1011) phage-displayed single-chain variable fragment (scFv) library, a fully human antibody, B11, which bound with high avidity (KD=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.

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