Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review
Cancer is the leading cause of death globally after cardiovascular diseases. Conventional therapeutic strategies have had minimal success rate. Recently, immunotherapy, particularly chimeric antigen receptor T cells (CAR T cells), has emerged as the most effective against cancer. A patient’s T lymph...
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Format: | Article |
Language: | English |
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Elsevier
2022-07-01
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Series: | Advances in Cancer Biology - Metastasis |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2667394022000090 |
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author | Ubaid Ahmad Zafran Khan Daniya Ualiyeva Obed Boadi Amissah Zohaib Noor Asaf Khan Nasib Zaman Marwa Khan Ayub Khan Babar Ali |
author_facet | Ubaid Ahmad Zafran Khan Daniya Ualiyeva Obed Boadi Amissah Zohaib Noor Asaf Khan Nasib Zaman Marwa Khan Ayub Khan Babar Ali |
author_sort | Ubaid Ahmad |
collection | DOAJ |
description | Cancer is the leading cause of death globally after cardiovascular diseases. Conventional therapeutic strategies have had minimal success rate. Recently, immunotherapy, particularly chimeric antigen receptor T cells (CAR T cells), has emerged as the most effective against cancer. A patient’s T lymphocytes have artificial chimeric antigen receptors genetically engineered on their surfaces to target specific antigens present on the surfaces of the cancer cell. A typical chimeric antigen receptor includes four domains, each of which serves a distinct purpose; the antigen recognition domain at the exterior of the cell is responsible for antigen recognition, the hinge region and transmembrane domain provides stability whereas, the intracellular domain in the endodomain of the receptor plays a crucial role in transmitting signals to activate the effector function of CAR T cells. Since CARs discovery, many properties have been added to CAR T cells to improve their effectiveness against the cancer. CAR T cell manufacturing processes involve; Isolation of lymphocytes, T cell selection and expansion, Gene transfer, formulation, quality assurance, and T cell infusion. Each of these CAR T cell engineering steps requires rigorous experimental processes done by a skillful team of researchers. A mistake during the manufacturing process may result in life-threatening consequences. Despite CAR T effectiveness, it imposes severe and unwanted side effect such as Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). As a result, CAR T-cell therapy must be accompanied by prompt treatment of the imminent side effects that may arise. |
first_indexed | 2024-12-12T16:31:41Z |
format | Article |
id | doaj.art-52c40b27adc343cca63a532a7ed84cba |
institution | Directory Open Access Journal |
issn | 2667-3940 |
language | English |
last_indexed | 2024-12-12T16:31:41Z |
publishDate | 2022-07-01 |
publisher | Elsevier |
record_format | Article |
series | Advances in Cancer Biology - Metastasis |
spelling | doaj.art-52c40b27adc343cca63a532a7ed84cba2022-12-22T00:18:46ZengElsevierAdvances in Cancer Biology - Metastasis2667-39402022-07-014100035Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive reviewUbaid Ahmad0Zafran Khan1Daniya Ualiyeva2Obed Boadi Amissah3Zohaib Noor4Asaf Khan5Nasib Zaman6Marwa Khan7Ayub Khan8Babar Ali9Center for Biotechnology and Microbiology, University of Swat, PakistanCenter for Biotechnology and Microbiology, University of Swat, Pakistan; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.University of Chinese Academy of Sciences, Beijing, 100049, China; Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China; Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan; Corresponding author. Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan.University of Chinese Academy of Sciences, Beijing, 100049, ChinaUniversity of Chinese Academy of Sciences, Beijing, 100049, China; Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaMinistry of Education, Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, 730000, Gansu, ChinaCenter for Biotechnology and Microbiology, University of Swat, PakistanDepartment of Optometry, Isra University Islamabad, PakistanComputer and Software Technology, University of Swat, PakistanDepartment of Optometry, Isra University Islamabad, PakistanCancer is the leading cause of death globally after cardiovascular diseases. Conventional therapeutic strategies have had minimal success rate. Recently, immunotherapy, particularly chimeric antigen receptor T cells (CAR T cells), has emerged as the most effective against cancer. A patient’s T lymphocytes have artificial chimeric antigen receptors genetically engineered on their surfaces to target specific antigens present on the surfaces of the cancer cell. A typical chimeric antigen receptor includes four domains, each of which serves a distinct purpose; the antigen recognition domain at the exterior of the cell is responsible for antigen recognition, the hinge region and transmembrane domain provides stability whereas, the intracellular domain in the endodomain of the receptor plays a crucial role in transmitting signals to activate the effector function of CAR T cells. Since CARs discovery, many properties have been added to CAR T cells to improve their effectiveness against the cancer. CAR T cell manufacturing processes involve; Isolation of lymphocytes, T cell selection and expansion, Gene transfer, formulation, quality assurance, and T cell infusion. Each of these CAR T cell engineering steps requires rigorous experimental processes done by a skillful team of researchers. A mistake during the manufacturing process may result in life-threatening consequences. Despite CAR T effectiveness, it imposes severe and unwanted side effect such as Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). As a result, CAR T-cell therapy must be accompanied by prompt treatment of the imminent side effects that may arise.http://www.sciencedirect.com/science/article/pii/S2667394022000090Chimeric antigen receptorCAR T-cellCancerCytokine release syndromeLymphocytesand Immune effector cell-associated neurotoxicity syndrome |
spellingShingle | Ubaid Ahmad Zafran Khan Daniya Ualiyeva Obed Boadi Amissah Zohaib Noor Asaf Khan Nasib Zaman Marwa Khan Ayub Khan Babar Ali Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review Advances in Cancer Biology - Metastasis Chimeric antigen receptor CAR T-cell Cancer Cytokine release syndrome Lymphocytes and Immune effector cell-associated neurotoxicity syndrome |
title | Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review |
title_full | Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review |
title_fullStr | Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review |
title_full_unstemmed | Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review |
title_short | Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review |
title_sort | chimeric antigen receptor t cell structure its manufacturing and related toxicities a comprehensive review |
topic | Chimeric antigen receptor CAR T-cell Cancer Cytokine release syndrome Lymphocytes and Immune effector cell-associated neurotoxicity syndrome |
url | http://www.sciencedirect.com/science/article/pii/S2667394022000090 |
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