Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products

Pharm Res. 2021 Jun;38(6):931-945. doi: 10.1007/s11095-021-03067-z. Epub 2021 Jun 10.

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T cell source used in CAR-T cell therapy is derived predominantly from the patient's own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. The generation of autologous CAR-T cells is time-consuming due to the lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), can provide an unlimited T cell source for CAR-T cell development with the potential of generating off-the-shelf T cell products. T-iPSCs (iPSC-derived T cells) are phenotypically defined, expandable, and as functional as physiological T cells. The combination of iPSC and CAR technologies provides an exciting opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. However, T-iPSCs, in combination with CARs, are at the early stage of development and need further pre-clinical and clinical studies. This review will critically discuss the progress made in iPSC-derived T cells and provides a roadmap for the development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs.

Keywords: CAR-T cell; T cell; iPSC; iPSC-derived T cell; off-the-shelf, stem cells; tumor cell.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy / methods*
  • Cell- and Tissue-Based Therapy / trends
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / trends
  • Induced Pluripotent Stem Cells / immunology
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / metabolism
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*

Substances

  • Receptors, Chimeric Antigen