Accelerating T Cell Receptor–mimic (TCRm) Antibody Discovery and Optimization via Mammalian Cell–Based Directed Evolution and AI/ML-guided Digital Design
- T cell receptor mimic antibodies enable therapeutic targeting of intracellular antigens through peptide MHC complexes that are inaccessible to conventional antibodies
- Discovery is challenging due to the need for extreme specificity across closely related peptide MHC epitopes, modest binding affinities, and preservation of native peptide presentation during screening
- Integrating high diversity immune libraries with advanced mammalian cell sorting using target expressing cells to identify potent, selective, and developable TCRm antibodies
- Display platforms enable detailed mapping of peptide specificity, while AI/ML guided protein engineering accelerates optimization of affinity, selectivity, safety, and developability from early binders to therapeutic candidates