Redirecting T cells to tumor targets with functionally diverse CD3-binding antibodies
DeVorkin L, et al. American Association for Cancer Research® (AACR) Annual Meeting, April 2022
This poster describes a panel of CD3-binding antibodies to support identification of effective T-cell engagers. Bioinformatic analysis of 275 unique CD3-binding antibody sequences revealed high sequence diversity, including a range of CDR3 lengths and V gene usage. Further, the panel showed functional diversity, with a broad range of CD3 affinities and T-cell activation potencies. Biophysical characterization demonstrated that CD3-binding antibodies have favorable developability properties, including low mean hydrophobicity, self-association, and polyspecificity. In a proof-of-concept study, CD3-binding antibodies were paired with a single EGFR-binding arm using the OrthoMab™ bispecifics platform. The resulting bispecific antibodies activated T cells with a range of potencies and led to T cell-mediated tumor-cell killing of EGFR-expressing cell lines.
