mechano-optimized TCR-T cells targeting KRAS-G12D

Mechano-optimized TCR-T cells targeting KRAS-G12D are a next-generation T-cell receptor engineered T-cell (TCR-T) therapy developed using a rational design platform focused on TCR-pMHC mechano-dynamics. Unlike conventional high-affinity engineered TCRs that often possess rigid binding interfaces, these cells utilize TCRs engineered to maintain the flexible binding interface and force-stabilized "catch bond" behavior characteristic of natural T-cell receptors. This mechano-optimization significantly enhances antigen sensitivity (approximately 40-fold higher than conventional high-affinity TCRs) and specificity for the KRAS-G12D neoantigen presented by HLA-A*11:01. Preclinical studies indicate that these TCR-T cells exhibit superior serial tumor killing, reduced exhaustion (marked by lower PD-1 expression), and enhanced differentiation into long-lived memory phenotypes. In KRAS-G12D xenograft models, the therapy achieved robust tumor clearance and demonstrated high specificity with no detectable cross-reactivity to wild-type KRAS or other human proteome proteins.

Other names

mechano-optimized TCR-T cells targeting KRAS-G12D