T-cell engagers targeting pMHCs must have a high degree of specificity to a small (~10 amino acid) peptide while avoiding substantial interactions with the MHC to minimize the risk of off-target toxicities. In addition, they need to bind to tumor cells expressing low levels of the target while working in concert with the CD3-binding arm to induce tumor-cell killing.

By combining our T-cell engager platform, which includes hundreds of diverse CD3-binding antibodies, with our antibody discovery, engineering, and development capabilities, we have built a platform capable of overcoming the challenges that have limited development of pMHC-targeting T-cell engagers. In this case study, we present data demonstrating how we leveraged our platform to discover functional and specific T-cell engager molecules targeting the pMHC melanoma-associated antigen 4 (MAGE-A4).