Exploiting natural killer group 2D receptors for CAR T-cell therapy

Future Oncol. 2017 Aug;13(18):1593-1605. doi: 10.2217/fon-2017-0102. Epub 2017 Jun 14.

Abstract

Chimeric antigen receptors (CARs) are genetically engineered proteins that combine an extracellular antigen-specific recognition domain with one or several intracellular T-cell signaling domains. When expressed in T cells, these CARs specifically trigger T-cell activation upon antigen recognition. While the clinical proof of principle of CAR T-cell therapy has been established in hematological cancers, CAR T cells are only at the early stages of being explored to tackle solid cancers. This special report discusses the concept of exploiting natural killer cell receptors as an approach that could broaden the specificity of CAR T cells and potentially enhance the efficacy of this therapy against solid tumors. New data demonstrating feasibility of this approach in humans and supporting the ongoing clinical trial are also presented.

Keywords: CAR-T; CM-CS1; NKG2D; NKR-2; adoptive cell therapy; chimeric antigen receptor; clinical trial; immunotherapy; pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Clinical Trials as Topic
  • Cytotoxicity, Immunologic
  • Drug Evaluation, Preclinical
  • Humans
  • Immunotherapy, Adoptive* / methods
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell