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...

Full description

Bibliographic Details
Main Authors: Ubaid Ahmad, Zafran Khan, Daniya Ualiyeva, Obed Boadi Amissah, Zohaib Noor, Asaf Khan, Nasib Zaman, Marwa Khan, Ayub Khan, Babar Ali
Format: Article
Language:English
Published: Elsevier 2022-07-01
Series:Advances in Cancer Biology - Metastasis
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667394022000090
_version_ 1818252910901854208
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
work_keys_str_mv AT ubaidahmad chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT zafrankhan chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT daniyaualiyeva chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT obedboadiamissah chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT zohaibnoor chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT asafkhan chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT nasibzaman chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT marwakhan chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT ayubkhan chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview
AT babarali chimericantigenreceptortcellstructureitsmanufacturingandrelatedtoxicitiesacomprehensivereview