Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy

Nat Biotechnol. 2013 Oct;31(10):928-33. doi: 10.1038/nbt.2678. Epub 2013 Aug 11.

Abstract

Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available, antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an unlimited source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain. Here we combine induced pluripotent stem cell (iPSC) and chimeric antigen receptor (CAR) technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture. These iPSC-derived, CAR-expressing T cells display a phenotype resembling that of innate γδ T cells. Similar to CAR-transduced, peripheral blood γδ T cells, the iPSC-derived T cells potently inhibit tumor growth in a xenograft model. This approach of generating therapeutic human T cells 'in the dish' may be useful for cancer immunotherapy and other medical applications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD19 / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Chromium Radioisotopes
  • Cluster Analysis
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Male
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Phenotype
  • Protein Engineering
  • Receptors, Antigen
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD19
  • Chromium Radioisotopes
  • Receptors, Antigen

Associated data

  • GEO/GSE47920