Targeting intracellular tumor antigens to fight cancer: discovery and development of functional and specific T-cell engagers against a MAGE-A4 pMHC

Tortora D, et al. Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 2023

This poster describes an integrated technology platform to streamline the discovery, engineering, and high-throughput assessment of T-cell engagers (TCEs) against intracellular tumor peptides displayed on major histocompatibility complexes (pMHCs). New data shows strategic selection and pairing of MAGE-A4-pMHC binders with antibodies from AbCellera’s CD3 platform to generate hundreds of MAGE-A4 x CD3 TCEs. Following high-throughput, multi-parameter functional, and specificity assessments, 12 MAGE-A4 x CD3 TCEs with potent T-cell-mediated tumor-cell killing, low cytokines, and high MAGE-A4-pMHC-binding specificity were identified. In addition, high-resolution structural assessment demonstrates diverse antibody binding orientations to MAGE-A4-pMHC. 

DOI: 10.1136/jitc-2023-SITC2023.1395

Further reading:

1. Tortora D, et al. Cancer Res (2024) 84 (6_Supplement): 2373.
2. Tortora D, et al. Cancer Res (2023) 83 (7_Supplement): 1891.