CD3 T-cell engagers (TCEs) targeting prostate-specific membrane antigen (PSMA) have emerged as a promising approach for the treatment of metastatic castration-resistant prostate cancer. In this case study, we present a function-first approach to identify TCEs and address the clinical challenges observed in PSMA-targeted bispecifics.

Starting with highly diverse CD3- and PSMA-binding antibodies, we identified TCEs that show significantly lower cytokine release than clinical benchmarks, while maintaining potent killing of PSMA-expressing cancer cell lines in vitro.