Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies.The four classes are: Extranodal T cell lymphoma Cutaneous T cell lymphomas: Sézary syndrome and Mycosis fungoides Anaplastic large cell lymphoma Angioimmunoblastic T-cell lymphoma

Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies.:

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Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies.

Stem Cell Rev Rep. 2020 Feb 01;:

Authors: Wada M, Zhang H, Fang L, Feng J, Tse CO, Zhang W, Chen Q, Sha S, Cao Y, Chen KH, Pinz KG, Chen X, Fan XX, Jiang X, Ma Y

Abstract

T-cell malignancies often result in poor prognosis and outcome for patients. Immunotherapy has recently emerged as a revolutionary treatment against cancer, and the success seen in CD19 CAR clinical trials may extend to T cell diseases. However, a shared antigen pool coupled with the impact of T-cell depletion incurred by targeting T cell disease remain concepts to be clinically explored with caution. Here we report on the ability of T cells transduced with a CD5CAR to specifically and potently lyse malignant T-cell lines and primary tumors in vitro in addition to significantly improving in vivo control and survival of xenograft models of T-ALL. To extensively explore and investigate the biological properties of a CD5 CAR, we evaluated multiple CD5 CAR constructs and constructed 3 murine models to characterize the properties of CD5 down-regulation, the efficacy and specificity produced by different CD5 CAR construct designs, and the impact of incorporating a CD52 safety switch using CAMPATH to modulate the persistency and function of CAR cells. These data support the potential use of CD5CAR T cells in the treatment of T cell malignancies or refractory disease in clinical settings.

PMID: 32008159 [PubMed - as supplied by publisher]