Gene-knocked out chimeric antigen receptor (CAR) T cells: Tuning up for the next generation cancer immunotherapy

Cancer Lett. 2018 Jun 1:423:95-104. doi: 10.1016/j.canlet.2018.03.010. Epub 2018 Mar 12.

Abstract

Recently clinical trials utilizing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that is half monoclonal antibody and half T-cell receptor have demonstrated remarkable response in patients with advanced cancers like relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoma. Moreover, emerging chimeric genome editing tools such as zinc-finger nucleases (ZNFs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas composed of sequence-specific DNA binding module(s) linked to a non-specific DNA cleavage domain have made possible to dramatically expand the ability to manipulate cells aim to treat and/or study a wide range of diseases including cancer. Here, we will discuss how joint application of these two chimeras will help us to manipulate CAR T cells aiming to enhance the efficacy of CAR T cell therapy in preclinical and clinical settings.

Keywords: Cancer immunotherapy; Chimeric antigen receptor T cells; Chimeric nucleases.

Publication types

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

MeSH terms

  • Clinical Trials as Topic
  • Gene Editing
  • Gene Knockout Techniques / methods*
  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Receptors, Chimeric Antigen / genetics*
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment

Substances

  • Receptors, Chimeric Antigen