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Chimeric Antigen Receptors for T-Cell Malignancies.

ABSTRACT: Development of chimeric antigen receptor (CAR)-modified T cells for the treatment of T-lineage leukemia and lymphoma has encountered several unique challenges. The most widely expressed tumor antigen targets for malignant T cells are often also expressed on non-malignant T cells. Transducing T cells with CARs targeted to these shared antigens can therefore promote over-activation or fratricide of CAR T cells, reducing their therapeutic potency. If fratricide is resolved, clinical CAR T cell activity may eliminate normal T-cell subsets and cause temporary immunosuppression. In this review, we summarize the preclinical development of CAR-based therapies for T-cell malignancies and discuss strategies to minimize toxicities associated with on-target fratricide and off-tumor activity.

SUBMITTER: Scherer LD

PROVIDER: S-EPMC6411696 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Chimeric Antigen Receptors for T-Cell Malignancies.

Scherer Lauren D LD Brenner Malcolm K MK Mamonkin Maksim M

Frontiers in oncology 20190305

Development of chimeric antigen receptor (CAR)-modified T cells for the treatment of T-lineage leukemia and lymphoma has encountered several unique challenges. The most widely expressed tumor antigen targets for malignant T cells are often also expressed on non-malignant T cells. Transducing T cells with CARs targeted to these shared antigens can therefore promote over-activation or fratricide of CAR T cells, reducing their therapeutic potency. If fratricide is resolved, clinical CAR T cell acti ...[more]

PMID: 30891427

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