Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity

Mol Cancer. 2019 Aug 20;18(1):125. doi: 10.1186/s12943-019-1057-4.


Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines release syndrome and on-target off-tumor toxicity. In some clinical trials, patients quitted the treatment of CAR-T cells due to life-threatening toxicity. Seeking to alleviate these toxicities or prevent the occurrence, researchers have developed a number of safety strategies of CAR-T cells, including suicide genes, synthetic Notch receptor, on-switch CAR, combinatorial target-antigen recognition, bispecific T cell engager and inhibitory CAR. This review summarized the preclinical studies and clinical trials of the safety strategies of CAR-T cells and their respective strengths and weaknesses.

Keywords: Chimeric antigen receptor; Immunotherapy; Suicide gene; Synthetic notch receptor; Toxicity.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Immunotherapy, Adoptive / methods
  • Immunotherapy, Adoptive / standards
  • Models, Biological
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism*
  • Receptors, Notch
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transgenes


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