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

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.

Automated summary

The fully human antibody B11, with high avidity to CD276, was used to design a more effective B11-BiTE than 8H9-BiTE in targeting 14 different cancer cell lines, showing strong ADCC/ADCP capabilities.