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Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients

Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic...

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Autores principales: Marofi, Faroogh, Rahman, Heshu Sulaiman, Al-Obaidi, Zaid Mahdi Jaber, Jalil, Abduladheem Turki, Abdelbasset, Walid Kamal, Suksatan, Wanich, Dorofeev, Aleksei Evgenievich, Shomali, Navid, Chartrand, Max Stanley, Pathak, Yashwant, Hassanzadeh, Ali, Baradaran, Behzad, Ahmadi, Majid, Saeedi, Hossein, Tahmasebi, Safa, Jarahian, Mostafa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377882/
https://www.ncbi.nlm.nih.gov/pubmed/34412685
http://dx.doi.org/10.1186/s13287-021-02420-8
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author Marofi, Faroogh
Rahman, Heshu Sulaiman
Al-Obaidi, Zaid Mahdi Jaber
Jalil, Abduladheem Turki
Abdelbasset, Walid Kamal
Suksatan, Wanich
Dorofeev, Aleksei Evgenievich
Shomali, Navid
Chartrand, Max Stanley
Pathak, Yashwant
Hassanzadeh, Ali
Baradaran, Behzad
Ahmadi, Majid
Saeedi, Hossein
Tahmasebi, Safa
Jarahian, Mostafa
author_facet Marofi, Faroogh
Rahman, Heshu Sulaiman
Al-Obaidi, Zaid Mahdi Jaber
Jalil, Abduladheem Turki
Abdelbasset, Walid Kamal
Suksatan, Wanich
Dorofeev, Aleksei Evgenievich
Shomali, Navid
Chartrand, Max Stanley
Pathak, Yashwant
Hassanzadeh, Ali
Baradaran, Behzad
Ahmadi, Majid
Saeedi, Hossein
Tahmasebi, Safa
Jarahian, Mostafa
author_sort Marofi, Faroogh
collection PubMed
description Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.
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spelling pubmed-83778822021-08-23 Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients Marofi, Faroogh Rahman, Heshu Sulaiman Al-Obaidi, Zaid Mahdi Jaber Jalil, Abduladheem Turki Abdelbasset, Walid Kamal Suksatan, Wanich Dorofeev, Aleksei Evgenievich Shomali, Navid Chartrand, Max Stanley Pathak, Yashwant Hassanzadeh, Ali Baradaran, Behzad Ahmadi, Majid Saeedi, Hossein Tahmasebi, Safa Jarahian, Mostafa Stem Cell Res Ther Review Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy. BioMed Central 2021-08-20 /pmc/articles/PMC8377882/ /pubmed/34412685 http://dx.doi.org/10.1186/s13287-021-02420-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Marofi, Faroogh
Rahman, Heshu Sulaiman
Al-Obaidi, Zaid Mahdi Jaber
Jalil, Abduladheem Turki
Abdelbasset, Walid Kamal
Suksatan, Wanich
Dorofeev, Aleksei Evgenievich
Shomali, Navid
Chartrand, Max Stanley
Pathak, Yashwant
Hassanzadeh, Ali
Baradaran, Behzad
Ahmadi, Majid
Saeedi, Hossein
Tahmasebi, Safa
Jarahian, Mostafa
Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
title Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
title_full Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
title_fullStr Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
title_full_unstemmed Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
title_short Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
title_sort novel car t therapy is a ray of hope in the treatment of seriously ill aml patients
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377882/
https://www.ncbi.nlm.nih.gov/pubmed/34412685
http://dx.doi.org/10.1186/s13287-021-02420-8
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