Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer

Curr Hematol Malig Rep. 2017 Dec;12(6):522-529. doi: 10.1007/s11899-017-0417-7.

Abstract

Purpose of review: In this review, we discuss the most recent developments in gene-editing technology and discuss their application to adoptive T cell immunotherapy.

Recent findings: Engineered T cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations. Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH™ (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies. As CART19 enters routine clinical use, improving the efficacy of this exciting platform is the next step in broader application. Novel gene-editing technologies like CRISPR-Cas9 allow facile editing of specific genes within the genome, generating a powerful platform to further optimize the activity of engineered T cells.

Keywords: Adoptive cell therapy; CRISPR-Cas9; Chimeric antigen receptor T cells (CART); Gene-editing; Immunotherapy; PD-1; TALEN; Zinc-finger nucleases.

Publication types

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

MeSH terms

  • Gene Editing / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • T-Lymphocytes / immunology*