CELL INTELLIGENCE · 肿瘤细胞治疗研究

The efficacy of chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory acute myeloid leukemia (R/R AML) is limited by tumor heterogeneity, antigen evasion, and treatment-related toxicities. Gamma delta ( ) T cells mediate antitumor activity independent of MHC by sensing stress-induced ligands. A prominent mechanism involves NKG2D ligand (NKG2DL) recognition, which is highly upregulated in malignancies but generally low or restricted expression in healthy tissues under homeostatic conditions. In human peripheral blood, the V 2 subset represents the predominant population. V 2 T cells transduced with the NKG2D-CD3 construct, which incorporates into the natural TCR/CD3 complex, preserve innate phosphoantigen recognition while acquiring potent NKG2DL-directed cytotoxicity, enabling dual-pathway tumor recognition. These cells are termed "Super V 2 T cells." We successfully generated TRAC-specific integrated Super V 2 T cells using CRISPR/Cas9 technology, achieving 90-93% CAR + expression. In vitro assays demonstrated that the engineered "Super V 2 T cells" exhibited potent cytotoxic activity against multiple AML targets, including cell lines and primary R/R AML blasts, in contrast to their negligible toxicity on monocytes. In vivo, Super V 2 T cells demonstrated substantial tumor reduction without graft-versus-host disease (GvHD) reaction. Collectively, our data demonstrated that Super V 2 T cells represent a viable allogeneic therapy for AML.