Xiang J, Devenport JM, Carter AJ, et al. An 'Off-the-Shelf' CD2 Universal CAR-T Therapy for T-Cell Malignancies. Leukemia. 2023; (doi: 10.1038/s41375-023-02039-z).
Researchers suspect patients with T-cell malignancies would benefit from a universal chimeric antigen receptor (CAR) T cell therapy that targets CD2 rather than CD7. CD2 is present on nearly all T cells, while CD7 is missing or downregulated in certain diseases, promoting treatment resistance and/or relapse in some cases. Engineered using "off-the-shelf" CAR from allogeneic donors, the CD2 universal CAR (UCAR2) demonstrated promising activity against T-cell acute lymphoblastic leukemia (T-ALL) and cutaneous T-cell lymphoma (CTCL) in preclinical models. In vivo observations also revealed a survival benefit in tumor-engrafted NSG mice. To determine how CD2 influences CAR-T function, the team compared the anti-tumor efficacy of CD19 CAR-T cells with CD2 either deleted or left intact. Biallelic CD2 deletion addresses the threat of fratricide to healthy cells, but it weakened the potency of anti-tumor effect versus leaving CD2 in place. Researchers found a solution in the administration of rhIL-7-hyFc, which prolonged UCART2 persistence and improved in vivo survival. The combination of UCART2 and rhIL-7-hyFc delivered durable, complete responses in T-ALL and CTCL, but investigators believe it has strong potential for a wide range of other T-cell cancers.