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.

DOI: 10.1158/1538-7445.AM2022-312

Further reading:

1. Bergqvist P, et al. J Immunother Cancer 2024;12(Suppl 2):A1–A1683.
2. Mai M, et al. Cancer Res (2024) 84 (6_Supplement): 1868.
3. Mai M, et al. J Immunother Cancer 2023;11(Suppl 1):A1–A1731.
4. Mai M, et al. Cancer Res (2023) 83 (7_Supplement): 1886. 
5. DeVorkin L, et al. J Immunother Cancer (2022)10 (Suppl 2):A1–A1603.