Advancing cell-based cancer immunotherapy through stem cell engineering

Cell Stem Cell. 2023 May 4;30(5):592-610. doi: 10.1016/j.stem.2023.02.009. Epub 2023 Mar 21.

Abstract

Advances in cell-based therapy, particularly CAR-T cell therapy, have transformed the treatment of hematological malignancies. Although an important step forward for the field, autologous CAR-T therapies are hindered by high costs, manufacturing challenges, and limited efficacy against solid tumors. With ongoing progress in gene editing and culture techniques, engineered stem cells and their application in cell therapy are poised to address some of these challenges. Here, we review stem cell-based immunotherapy approaches, stem cell sources, gene engineering and manufacturing strategies, therapeutic platforms, and clinical trials, as well as challenges and future directions for the field.

Keywords: CRISPR-Cas9; T cell; T cell receptor; allogeneic off-the-shelf cell therapy; allorejection; cancer immunotherapy; chimeric antigen receptor; embryonic stem cell; feeder-free culture; gamma delta T cell; gene engineering; graft-versus-host disease; hematopoietic stem cell; immune cell; induced pluripotent stem cell; invariant natural killer T cell; lentivector; mucosal-associated invariant T cell; natural killer cell; stem cell.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Engineering
  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive / methods
  • Neoplasms* / therapy
  • Receptors, Chimeric Antigen* / genetics

Substances

  • Receptors, Chimeric Antigen