Development of a Novel Claudin 6-targeting CAR-T Cell Therapy

Abstract

Chimeric antigen receptor (CAR)-T cell therapies have demonstrated remarkable success in B-cell malignancies but have yet to show comparable outcomes in solid tumors. A major obstacle is the scarcity of tumor-specific antigens that enable precise and effective targeting. Claudin 6 (CLDN6), an oncofetal tight junction protein, serves as a promising target due to its aberrant upregulation in several solid tumors and absence in healthy adult tissues. In this study, we identified two CLDN6-specific antibodies and leveraged them to generate two second-generation CAR-T cells. Both constructs selectively eliminated CLDN6-positive tumor cells in vitro, while exhibiting distinct profiles in terms of efficacy and specificity. These findings present a promising avenue for developing next-generation immunotherapies for CLDN6-expressing solid tumors and provide a foundation for further development of CAR-T therapy in the treatment of solid tumors.