Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.

Shah, Zahir; Tian, Lei; Caligiuri, Michael A; Kaufman, Dan S; Yu, Jianhua · Cell Stem Cell · 2026

review · Level V

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Abstract

Allogeneic cell-based therapies hold great promise for cancer immunotherapy but face challenges like scalability, immune rejection, graft-versus-host disease, and toxicities. Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells (iPSCs), offer a scalable and adaptable platform to address these limitations. hPSCs provide an inexhaustible source of immune cells that can be genetically modified at the single-cell level to enhance anti-tumor activity and reduce immunogenicity. Recent advancements in generating iPSC-derived natural killer (NK) cells, T cells, and macrophages are opening the door to safer and more effective immunotherapies. This review examines the progress, challenges, and future directions in utilizing hPSC-derived immune cells to enhance cancer treatment and overcome barriers in allogeneic therapy.

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