KIR3DL2 CAR-T

KIR3DL2 CAR-T is a novel allogeneic Chimeric Antigen Receptor (CAR)-T cell therapy developed for the treatment of relapsed/refractory T cell lymphoma (TCL), including both peripheral and cutaneous TCL. This therapy addresses the challenges of CAR-T development for TCL, such as on-target off-tumor toxicities, difficulties in manufacturing autologous CAR-T cells from patients with compromised T cells, and antigen escape. The CAR-T cells are engineered to specifically target the KIR3DL2 receptor, which is highly expressed on TCL tumor cells but rarely on healthy T and NK cells. Utilizing a CRISPR-Homology Direct Repair (HDR) technology, the CAR gene is knocked into the TRAC locus and the HLA-E gene into the B2M locus, enabling the generation of 'off-the-shelf' allogeneic CAR-T cells. Preclinical studies have demonstrated superior efficacy and tumor specificity, with significant tumor control and complete tumor resolution in aggressive mouse models of TCL. The platform also incorporates epigenetic drug screening to identify agents that can upregulate KIR3DL2 expression on tumor cells, further enhancing the CAR-T cell efficacy against antigen-low tumors.