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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., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Although CAR T-cell therapy is US Food and Drug Administration-approved for B-cell non-Hodgkin lymphomas, the development of adoptive immunotherapy for the treatment of classic Hodgkin lymphoma (cHL) has not accelerated at a similar pace. Adoptive T-cell therapy with Epstein-Barr virus-specific cytotoxic T lymphocytes and CD30 CAR T cells have demonstrated significant clinical responses in early clinical trials of patients with cHL. Additionally, CD19 and CD123 CAR T cells that target the immunosuppressive tumor microenvironment in cHL have also been investigated. Here we discuss the landscape of clinical trials of adoptive immunotherapy for patients with cHL with a view toward current challenges and novel strategies to improve the development of CAR T-cell therapy for cHL., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Thirty years after initial publications of the concept of a chimeric antigen receptor (CAR), the U.S. Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell therapy. Unlike other immunotherapies, such as immune checkpoint inhibitors and bispecific antibodies, CAR T cells are unique as they are "living drugs," that is, gene-edited killer cells that can recognize and kill cancer. During these 30 years of development, the CAR construct, T-cell manufacturing process, and clinical patient management have gone through rounds of failures and successes that drove continuous improvement. Tisagenlecleucel was the first gene therapy to receive approval from the FDA for any indication. The initial approval was for relapsed or refractory (r/r) pediatric and young-adult B-cell acute lymphoblastic leukemia in August 2017 and in May 2018 for adult r/r diffuse large B-cell lymphoma. Here we review the preclinical and clinical development of what began as CART19 at the University of Pennsylvania and later developed into tisagenlecleucel., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that engineered immune cells can serve as a powerful new class of cancer therapeutics. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Advances in T cell engineering, genetic editing, the selection of optimal lymphocytes, and cell manufacturing have the potential to broaden T cell-based therapies and foster new applications beyond oncology, in infectious diseases, organ transplantation, and autoimmunity.