Abstract
Dual-attribute immune cells possess advantageous features of cytotoxic Tcells and natural killer (NK) cells and hold promise for advancing immunotherapy. Dual-attribute cell types such as invariant natural killer Tcells, induced T-to-NK cells, and cytokine-induced killer cells have demonstrated efficacy and safety in preclinical and clinical studies. However, their limited availability hinders their widespread application. Human pluripotent stem cells (hPSCs) offer an ideal source. Here, we generate dual-attribute induced T-NK (iTNK) cells from hPSCs, expressing markers of both cytotoxic T and NK cells. Single-cell RNA and Tcell receptor (TCR) sequencing analyses reveal that iTNK cells expressed signature genes associated with both NK and Tcells and displayed a diverse TCR repertoire. iTNK cells release cytotoxic mediators, exert cytotoxicity against diverse tumor cell lines, and inhibit tumor growth invivo. By harnessing adaptive and innate immune responses, hPSC-derived iTNK cells offer promising strategies for cancer immunotherapy.
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