Challenges of CAR T-cell Therapy in CLL: Lessons Learned

Abstract

Development of chimeric antigen receptor T (CART) cell therapy has led to unprecedented success against B cell leukemia and lymphoma and resulted in FDA-approved treatment protocols. Despite the initial clinical response in B cell-related malignancies, high relapse rates suggest that much work is needed to uncover mechanisms of resistance. In chronic lymphocytic leukemia (CLL), the durable activity of CAR T-cells is limited, and CART cell success is lower than in other malignancies. T cells from these patients are vulnerable to a state of dysfunction due to stresses including chronic infection, rapid cell cycle upon antigen recognition, immunosuppressive tumor microenvironment, and cancer-related treatments. T cells are also introduced to additional stresses when cultured ex vivo during the CART manufacturing process. All these factors contribute to the limited regenerative capacity of T cells, which can lead to CART treatment failure. In this short report, we will review the challenges of CAR T-cell therapy in patients with CLL and discuss potential strategies to overcome these challenges.