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From bench to bedside: the history and progress of CAR T cell therapy

Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by the Food and Drug Administration in 2017 for the treatment of pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia. As of April...

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Autores principales: Mitra, Aroshi, Barua, Amrita, Huang, Luping, Ganguly, Siddhartha, Feng, Qin, He, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225594/
https://www.ncbi.nlm.nih.gov/pubmed/37256141
http://dx.doi.org/10.3389/fimmu.2023.1188049
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author Mitra, Aroshi
Barua, Amrita
Huang, Luping
Ganguly, Siddhartha
Feng, Qin
He, Bin
author_facet Mitra, Aroshi
Barua, Amrita
Huang, Luping
Ganguly, Siddhartha
Feng, Qin
He, Bin
author_sort Mitra, Aroshi
collection PubMed
description Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by the Food and Drug Administration in 2017 for the treatment of pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia. As of April 2023, six CAR T cell therapies have been approved, demonstrating unprecedented efficacy in patients with B-cell malignancies and multiple myeloma. However, adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity pose significant challenges to CAR T cell therapy. The severity of these adverse events correlates with the pretreatment tumor burden, where a higher tumor burden results in more severe consequences. This observation is supported by the application of CD19-targeted CAR T cell therapy in autoimmune diseases including systemic lupus erythematosus and antisynthetase syndrome. These results indicate that initiating CAR T cell therapy early at low tumor burden or using debulking strategy prior to CAR T cell infusion may reduce the severity of adverse events. In addition, CAR T cell therapy is expensive and has limited effectiveness against solid tumors. In this article, we review the critical steps that led to this groundbreaking therapy and explore ongoing efforts to overcome these challenges. With the promise of more effective and safer CAR T cell therapies in development, we are optimistic that a broader range of cancer patients will benefit from this revolutionary therapy in the foreseeable future.
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spelling pubmed-102255942023-05-30 From bench to bedside: the history and progress of CAR T cell therapy Mitra, Aroshi Barua, Amrita Huang, Luping Ganguly, Siddhartha Feng, Qin He, Bin Front Immunol Immunology Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by the Food and Drug Administration in 2017 for the treatment of pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia. As of April 2023, six CAR T cell therapies have been approved, demonstrating unprecedented efficacy in patients with B-cell malignancies and multiple myeloma. However, adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity pose significant challenges to CAR T cell therapy. The severity of these adverse events correlates with the pretreatment tumor burden, where a higher tumor burden results in more severe consequences. This observation is supported by the application of CD19-targeted CAR T cell therapy in autoimmune diseases including systemic lupus erythematosus and antisynthetase syndrome. These results indicate that initiating CAR T cell therapy early at low tumor burden or using debulking strategy prior to CAR T cell infusion may reduce the severity of adverse events. In addition, CAR T cell therapy is expensive and has limited effectiveness against solid tumors. In this article, we review the critical steps that led to this groundbreaking therapy and explore ongoing efforts to overcome these challenges. With the promise of more effective and safer CAR T cell therapies in development, we are optimistic that a broader range of cancer patients will benefit from this revolutionary therapy in the foreseeable future. Frontiers Media S.A. 2023-05-15 /pmc/articles/PMC10225594/ /pubmed/37256141 http://dx.doi.org/10.3389/fimmu.2023.1188049 Text en Copyright © 2023 Mitra, Barua, Huang, Ganguly, Feng and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Mitra, Aroshi
Barua, Amrita
Huang, Luping
Ganguly, Siddhartha
Feng, Qin
He, Bin
From bench to bedside: the history and progress of CAR T cell therapy
title From bench to bedside: the history and progress of CAR T cell therapy
title_full From bench to bedside: the history and progress of CAR T cell therapy
title_fullStr From bench to bedside: the history and progress of CAR T cell therapy
title_full_unstemmed From bench to bedside: the history and progress of CAR T cell therapy
title_short From bench to bedside: the history and progress of CAR T cell therapy
title_sort from bench to bedside: the history and progress of car t cell therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225594/
https://www.ncbi.nlm.nih.gov/pubmed/37256141
http://dx.doi.org/10.3389/fimmu.2023.1188049
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