Progress and Pitfalls of Chimeric Antigen Receptor T Cell Immunotherapy against T Cell Malignancies

Chimeric antigen receptor T cell (CAR -T) immunotherapy has revolutionized the treatment of relapsed and refractory B cell -derived hematologic malignancies. Currently, there are 6 Food and Drug Administration -approved commercial CAR -T products that target antigens exclusively expressed on malignant B cells or plasma cells. However, concurrent advancement for patients with rarer and more aggressive T cell -derived hematologic malignancies have not yet been achieved. CAR -T immunotherapies are uniquely limited by challenges related to CAR -T product manufacturing and intrinsic tumor biology. In this review tailored for practicing clinician -scientists, we discuss the major barriers of CAR -T implementation against T cell -derived neoplasms and highlight specific scientific advancements poised to circumvent these obstacles. We summarize salient early -stage clinical trials implementing novel CAR -T immunotherapies specifically for patients with relapsed and/or refractory T cell neoplasms. Finally, we highlight novel manufacturing and treatment strategies that are poised to have a meaningful future clinical impact. (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.