CAR Therapy for T-cell Malignancies

Abstract

The introduction of chimeric antigen receptor (CAR) immunotherapy has been revolutionary in the treatment of hematological malignancies [1]. Remarkable success has been achieved in the clinical treatment of B-cell malignancies through the use of CD19 CARs [2-7]. However, translation of CAR therapy for T-cell malignancies has been more difficult for several reasons. As the CAR cells predominantly used are T cells, a CAR T cell manufactured to target malignant T cells using T-cell markers is at risk for fratricide. This would prevent the expansion of the CAR T cell population necessary for proper tumor eradication. Additionally, as both malignant and non-malignant express these T-cell markers, there is concern that a T-cell-directed CAR cell would lead to T-cell deficiency and subsequent opportunistic infections.