Paving New Roads for CARs

Trends Cancer. 2019 Oct;5(10):583-592. doi: 10.1016/j.trecan.2019.09.005. Epub 2019 Oct 19.


Chimeric antigen receptor (CAR)-T cell therapy has had unprecedented impact in the treatment of hematological malignancies with few therapeutic options. However, it is clear that new strategies to enhance CAR-T cell function in solid tumors are needed to make these living drugs widely applicable. The roadblock in solid tumors has led to a surge in the development of strategies to enhance CAR-T cells through advanced receptor design, new tumor sensing mechanisms, coexpression of genes that improve T cell function or stimulate tumor immunity, and precise genome editing. Here we provide an overview of the current state of the art in CAR-T cell engineering and a framework for the development of next-generation immune cell therapies with synthetic biology.

Keywords: cancer immunology; cell therapy; chimeric antigen receptors; immune cell signaling; synthetic biology; tumor microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Genetic Engineering
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Tumor Microenvironment / immunology


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