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

Transl Oncol. 2021-10;

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

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Proteins, Expression, Isolation and Analysis	… The B11-IgG or BiTE proteins were expressed in the Expi293™ expression system (Thermo Fisher Scientific) and purified by protein A resin (GenScript, Piscataway, NJ). Protein purity was estimated as >95% and protein concentration was measured spectrophotometrically (…	Get A Quote

摘要

The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (10) phage-displayed single-chain variable fragment (scFv) library, a fully human antibody, B11, which bound with high avidity (K=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.