Understanding T cell phenotype for the design of effective chimeric antigen receptor T cell therapies

Rapid advances in immunotherapy have identified adoptive cell transfer as one of the most promising approaches for the treatment of cancers. Large numbers of cancer reactive T lymphocytes can be generated ex vivo from patient blood by genetic modification to express chimeric antigen receptors (CAR) specific for tumor-associated antigens. CAR T cells can respond strongly against cancer cells, and adoptive transferred CAR T cells can induce dramatic responses against certain types of cancers. The ability of T cells to respond against disease depends on their ability to localize to sites, persist and exert functions, often in an immunosuppressive microenvironment, and these abilities are reflected in their phenotypes. There is currently intense interest in generating CAR T cells possessing the ideal phenotypes to confer optimal antitumor activity. In this article, we review T cell phenotypes for trafficking, persistence and function, and discuss how culture conditions and genetic makeups can be manipulated to achieve the ideal phenotypes for antitumor activities.

Automated summary

Immunotherapy has identified adoptive cell transfer as a promising approach for treating cancers, generating cancer reactive CAR T cells through genetic modification to target tumor-associated antigens. The ability of CAR T cells to respond against disease depends on their phenotypes, with current interest in generating ideal phenotypes for optimal antitumor activity through manipulation of culture conditions and genetic makeups.