Antigen-IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα - PubMed
3 days ago
- #CAR-T therapy
- #Cancer immunotherapy
- #IL-2 signaling
- Antigen-IL-2 CAR-enhancer (CAR-E) enhances CAR-T persistence and function by fusing tumor antigens to IL-2 muteins.
- CAR-E activity is independent of IL-2Rα and critically dependent on IL-2Rβγ signaling.
- Next-generation IL-2Rα-sparing CAR-E maintains full potency, driving robust CAR-T expansion, persistence, and tumor clearance.
- CAR-T cells resist exhaustion and re-expand months later to eradicate tumor rechallenges.
- In humanized mice, CAR-Es selectively expand CAR-Ts to dominate the circulating T-cell pool.
- CAR-E overrides tumor-derived cues, enforcing consistent phenotypes across diverse preclinical models.
- Findings nominate a lead BCMA-IL-2 CAR-E candidate for clinical development.
- IL-2Rβγ identified as a key driver of CAR-E activity, with IL-2Rα being dispensable.