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Development of CAR T cells designed to improve antitumor efficacy and safety.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models.

SUBMITTER: Jaspers JE

PROVIDER: S-EPMC5601024 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Development of CAR T cells designed to improve antitumor efficacy and safety.

Jaspers Janneke E JE Brentjens Renier J RJ

Pharmacology & therapeutics 20170322

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how opt ...[more]

PMID: 28342824

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