A novel KIR3DL2-directed CAR T-cell therapy for cutaneous and systemic T-cell lymphomas

KIR3DL2-directed CAR T cells (3DL2CARs) produced sustained tumor regression and prolonged survival in xenograft models of cutaneous and hepatosplenic T-cell lymphomas.

• Why it matters: Extending CAR T therapy to T-cell lymphomas is limited by few safe targets, and pan–T-cell antigen approaches risk immunosuppression and infection.
• What they did: Single-cell RNA-seq and flow cytometry showed KIR3DL2 is largely restricted to a subset of mature NK cells and a minor fraction of CD8 T cells, with low expression in other adult tissues; 3DL2CARs selectively triggered antigen-positive tumor killing and cytokine responses.
• The result: 3DL2CART cells showed minimal off-target effects and no appreciable fratricide, and a two-tier manufacturing strategy (KIR3DL2-positive tumor depletion plus an in vivo safety switch) supported preclinical efficacy and safety.

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