Clinical practice: chimeric antigen receptor (CAR) T cells: a major breakthrough in the battle against cancer
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REVIEW ARTICLE
Clinical practice: chimeric antigen receptor (CAR) T cells: a major breakthrough in the battle against cancer Stefan Lundh1 · In‑Young Jung1,2,3 · Alexander Dimitri1,2,3 · Anish Vora1 · J. Joseph Melenhorst1,3,4,5 · Julie K. Jadlowsky1 · Joseph A. Fraietta1,2,3,4,5 Received: 7 November 2019 / Accepted: 7 April 2020 © Springer Nature Switzerland AG 2020
Abstract Chimeric antigen receptor (CAR) T cell therapy has come of age, offering a potentially curative option for patients who are refractory to standard anti-cancer treatments. The success of CAR T cell therapy in the setting of acute lymphoblastic leukemia and specific types of B cell lymphoma led to rapid regulatory approvals of CD19-directed CAR T cells, first in the United States and subsequently across the globe. Despite these major milestones in the field of immuno-oncology, growing experience with CAR T cells has also highlighted the major limitations of this strategy, namely challenges associated with manufacturing a bespoke patient–specific product, intrinsic immune cell defects leading to poor CAR T cell function as well as persistence, and/or tumor cell resistance resulting from loss or modulation of the targeted antigen. In addition, both onand off-tumor immunotoxicities and the financial burden inherent in conventional cellular biomanufacturing often hamper the success of CAR T cell-based treatment approaches. Herein, we provide an overview of the opportunities and challenges related to the first form of gene transfer therapy to gain commercial approval in the United States. Ongoing advances in the areas of genetic engineering, precision genome editing, toxicity mitigation methods and cell manufacturing will improve the efficacy and safety of CAR T cells for hematologic malignancies and expand the use of this novel class of therapeutics to reach solid tumors. Keywords Chimeric antigen receptor · CAR T cell · Cancer · Immunotherapy
Introduction
* Joseph A. Fraietta [email protected] 1
Center for Cellular Immunotherapies, University of Pennsylvania, South Pavilion Expansion, Room 9‑104, 3400 Civic Center Blvd., Bldg. 421, Philadelphia, PA 19104, USA
2
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
3
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
4
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
5
Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA, USA
The field of cancer immunotherapy has undergone transformative changes over the last several years and is currently progressing at an unprecedented pace to further advance recent therapeutic successes. Much enthusiasm related to harnessing the power of the immune system to reduce unmet medical needs in hematologic malignancies and solid tumors has been attributed to the remarkable clinical results of checkpoint inhibitors and chimeric antigen receptor (CAR) T cells.
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