Chimeric antigen receptor T-cell therapy for T-cell acute lymphoblastic leukemia

Chimeric antigen receptor (CAR) T -cell therapy is a new and effective treatment for patients with hematologic malignancies. Clinical responses to CAR T cells in leukemia, lymphoma, and multiple myeloma have provided strong evidence of the antitumor activity of these cells. In patients with refractory or relapsed B -cell acute lymphoblastic leukemia (ALL), the infusion of autologous anti-CD19 CAR T cells is rapidly gaining standard -of -care status and might eventually be incorporated into frontline treatment. In T -ALL, however, leukemic cells generally lack surface molecules recognized by established CAR, such as CD19 and CD22. Such deficiency is particularly important, as outcome is dismal for patients with T -ALL that is refractory to standard chemotherapy and/or hematopoietic stem cell transplant. Recently, CAR T -cell technologies directed against T -cell malignancies have been developed and are beginning to be tested clinically. The main technical obstacles stem from the fact that malignant and normal T cells share most surface antigens. Therefore, CAR T cells directed against T -ALL targets might be susceptible to self -elimination during manufacturing and/or have suboptimal activity after infusion. Moreover, removing leukemic cells that might be present in the cell source used for CAR T -cell manufacturing might be problematic. Finally, reconstitution of T cells and natural killer cells after CAR T -cell infusion might be impaired. In this article, we discuss potential targets for CAR T -cell therapy of T -ALL with an emphasis on CD7, and review CAR configurations as well as early clinical results.