epidermal growth factor receptor-targeting third-generation chimeric antigen receptor t-cell + small molecule inhibitor

This preclinical combination therapy, developed by the National Institute of Diagnostics and Vaccine Development in Infectious Diseases (NIDVD) at Xiamen University, pairs third-generation chimeric antigen receptor T-cells (CAR-T) with a small molecule inhibitor of epigenetic modifiers. The CAR-T cells are engineered to target the epidermal growth factor receptor (EGFR) using a cetuximab-derived single-chain variable fragment (scFv) and contain a tripartite signaling domain consisting of CD28, 4-1BB, and CD3ζ. The therapy is primarily aimed at treating solid tumors, specifically triple-negative breast cancer (TNBC), where EGFR is frequently overexpressed. The addition of the small molecule inhibitor is designed to overcome CAR-T resistance by preventing the epigenetic remodeling and enhancer activation that leads to the expression of immunosuppressive genes in tumor cells.

Other names

EGFR 3rd-gen CAR-T (combination)EGFR-targeting 3rd-gen CAR-T + epigenetic modifier inhibitor