Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

Semin Immunopathol. 2019 Jan;41(1):59-68. doi: 10.1007/s00281-018-0721-x. Epub 2018 Oct 25.

Abstract

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic "universal" cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing.

Keywords: Cancer immunotherapy; Cell therapy; Chimeric antigen receptor; Induced pluripotent stem cells; Natural killer cells; Off-the-shelf.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement / immunology
  • Cell- and Tissue-Based Therapy* / methods
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / immunology
  • Cytotoxicity, Immunologic
  • Genetic Engineering
  • Humans
  • Immunotherapy, Adoptive / methods
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism
  • T-Cell Antigen Receptor Specificity / immunology

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen