Preclinical Development of T Cells Engineered to Express a T-Cell Antigen Coupler Targeting Claudin 18.2-Positive Solid Tumors.

ABSTRACT: The T-cell antigen coupler (TAC) is a chimeric receptor that facilitates tumor antigen-specific activation of T cells by co-opting the endogenous T-cell receptor complex in the absence of tonic signaling. Previous data demonstrate that the TAC affords T cells with the ability to induce durable and safe antitumor responses in preclinical models of hematologic and solid tumors. In this study, we describe the preclinical pharmacology and safety of an autologous Claudin 18.2 (CLDN18.2)-directed TAC T-cell therapy, TAC01-CLDN18.2, in preparation for a phase I/II clinical study in subjects with CLDN18.2-positive solid tumors. Following a screen of putative TAC constructs, the specificity, activity, and cytotoxicity of TAC T cells expressing the final CLDN18.2-TAC receptor were evaluated in vitro

SUBMITTER: Xu SX 

PROVIDER: S-EPMC11712040 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature