Mesh : Alemtuzumab / pharmacology therapeutic use Animals CD5 Antigens / metabolism Cell Line Down-Regulation / drug effects Humans Immunotherapy, Adoptive Male Mice Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy immunology therapy Recombinant Proteins / metabolism T-Lymphocytes / immunology Xenograft Model Antitumor Assays

来  源:   DOI:10.1007/s12015-019-09937-9   PDF(Sci-hub)

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.
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