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

Cell Stem Cell. 2026 Feb 5;33(2):184-201. doi: 10.1016/j.stem.2025.12.017. Epub 2026 Jan 8.

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.

Keywords: CAR-NK cells; CAR-T cells; CAR-macrophages; NK cells; T cells; allogeneic immune cells; cancer immunotherapy; hematopoiesis; human pluripotent stem cells; hypoimmune cells; innate immune cells; macrophages; off-the-shelf.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Humans
  • Immunity, Innate*
  • Immunotherapy* / methods
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / immunology
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Pluripotent Stem Cells* / cytology
  • Pluripotent Stem Cells* / immunology