Conditioned CAR-T cells (cirCAR-T) for enhanced tumor immmunotherapy

Objetivo

Chimeric antigen receptor T-cell (CAR-T) therapy is a breakthrough immunotherapy for aggressive blood cancers. With >250 companies active in the field, >1,200 CAR- T variants in clinical development, and a market exceeding $5B, CAR-T therapies represent an expanding biomedical sector. However, despite response rates of up to 90%, long-term remissions remain limited (30–40%), and efficacy in solid tumors remains poor, highlighting a major unmet medical need. Improving CAR-T cell potency, persistence, and functionality thus remains a central challenge. My ERC project CIRCADYN uncovered a previously unrecognised mechanism in regulating immune responses and immunotherapy efficacy. Building on these findings, we developed a novel strategy, termed cirCAR-T, which enhances CAR-T cell performance without additional genetic modification. Preliminary data demonstrate up to a 10-fold increase in tumor cell killing and up to a 9-fold increase in antigen-driven CAR-T cell proliferation. This Proof-of-Concept project will de-risk the translational potential of cirCAR-T through three complementary objectives: (i) demonstrating functional benefits in more physiologically relevant solid tumor contexts and evaluating initial safety signals; (ii) establishing a knowledge-transfer strategy through expert consultation to clarify regulatory classification, intellectual-property options, freedom-to-operate considerations, and (iii) mapping the most efficient commercialization pathways. Together, these activities will determine the feasibility of developing cirCAR-T as a novel enabling technology to enhance CAR-T cell potency and persistence and support their expansion toward broader clinical applications, including solid tumors.