Chimeric antigen receptor-T cell therapy for T cell-derived hematological malignancies

Abstract

Relapsed/refractory T cell-derived malignancies present with high heterogeneity and poor prognoses. Recently, chimeric antigen receptor (CAR)-T cell therapy has shown remarkable safety and efficacy in the treatment of B cell-derived malignancies. However, the treatment of CAR-T cells in T cell-derived malignancies has more limitations, such as fratricide, T cell aplasia, and tumor contamination, mainly because of the similarity between normal and malignant T cells. Pan-T antigen CAR-T cells (such as CD5 and CD7 targets), the most widely used CAR-T cells in clinical trials, can cover almost all T cell-derived malignant cells but can also induce severe killing of CAR-T cells and normal T cells. Compared to autologous sources of CAR-T cells, allogeneic CAR-T cells can prevent tumor contamination and become universal products by gene-editing. However, none of these CAR-T cells could completely prevent immune deficiency and disease relapse after T-targeted CAR-T cell therapy. In this review, we summarize the current challenges of CAR-T cell therapy for T cell-derived malignancies in clinical practice and potential strategies to address these limitations.