Navigating CAR-T cells through the solid-tumour microenvironment

Nat Rev Drug Discov. 2021 Jul;20(7):531-550. doi: 10.1038/s41573-021-00189-2. Epub 2021 May 10.

Abstract

The adoptive transfer of T cells that are engineered to express chimeric antigen receptors (CARs) has shown remarkable success in treating B cell malignancies but only limited efficacy against other cancer types, especially solid tumours. Compared with haematological diseases, solid tumours present a unique set of challenges, including a lack of robustly expressed, tumour-exclusive antigen targets as well as highly immunosuppressive and metabolically challenging tumour microenvironments that limit treatment safety and efficacy. Here, we review protein- and cell-engineering strategies that seek to overcome these obstacles and produce next-generation T cells with enhanced tumour specificity and sustained effector function for the treatment of solid malignancies.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunotherapy, Adoptive*
  • Protein Engineering
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / immunology*

Substances

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