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The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead.

作者信息

Rohit Reddy Sai, Llukmani Adiona, Hashim Ayat, Haddad Dana R, Patel Dutt S, Ahmad Farrukh, Abu Sneineh Majdi, Gordon Domonick K

机构信息

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Internal Medicine, Scarborough General Hospital, Scarborough, TTO.

出版信息

Cureus. 2021 Feb 25;13(2):e13552. doi: 10.7759/cureus.13552.


DOI:10.7759/cureus.13552
PMID:33815972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8007123/
Abstract

Immunotherapy is the upcoming trend in cancer treatment. Traditional cancer treatment methods include surgical resection, radiotherapy, chemotherapy, small molecule targeted drugs, monoclonal antibodies, and hematopoietic stem cell transplantation (HSCT). Surgical resection is useful for early-stage patients but not for metastatic cancer cells; radiotherapy and chemotherapy are more common but produce substantial damage to normal tissues and have poor selectivity. Targeted drugs, including monoclonal antibodies, have better comprehensive efficacy but can also encourage gene mutation of tumor cells and drug tolerance. HSCT is effective, but choosing a donor is often difficult, and the graft is also prone to rejection. Thus, chimeric antigen receptor (CAR)-T cell therapy, a form of cellular/adoptive immunotherapy, is at the forefront of cancer therapy treatments due to its sustained remission, fewer side effects, and a better quality of life. CAR-T cell therapy involves genetically modifying the T cells and multiplying their numbers to kill cancer cells. This review article gives an insight into how the CAR-T cells have evolved from simple T cells with modest immune function to genetically engineered robust counterparts that brought great hope in the treatment of hematological malignancies. Much research has been undertaken during the past decade to design and deliver CAR-T cells. This has led to successful outcomes in leukemias, lymphomas, and multiple myeloma, paving the way for expanding CAR therapy. Despite tremendous progress, CAR-T cell therapies are faced with many challenges. Areas for improvement include limited T cell persistence, tumor escape, immunosuppressive components in the tumor microenvironment, cancer relapse rate, manufacturing time, and production cost. In this manuscript, we summarize the innovations in the design and delivery of CAR technologies, their applications in hematological malignancies, limitations to its widespread application, latest developments, and the future scope of research to counter the challenges and improve its effectiveness and persistence.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/e37ce0abafec/cureus-0013-00000013552-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/8d96c8aeb00b/cureus-0013-00000013552-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/3e1cbacb9443/cureus-0013-00000013552-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/2e06ca38d4d8/cureus-0013-00000013552-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/e37ce0abafec/cureus-0013-00000013552-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/8d96c8aeb00b/cureus-0013-00000013552-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/3e1cbacb9443/cureus-0013-00000013552-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/2e06ca38d4d8/cureus-0013-00000013552-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2812/8007123/e37ce0abafec/cureus-0013-00000013552-i04.jpg

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[1]
The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead.

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Int J Mol Cell Med. 2025-7-1

[2]
Altered dynamics of T cell subsets in peripheral blood impacts disease progression in newly diagnosed multiple myeloma.

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[3]
Colorectal Cancer: Risk Factors, Novel Approaches in Molecular Screening and Treatment.

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[4]
Tri-specific tribodies targeting 5T4, CD3, and immune checkpoint drive stronger functional T-cell responses than combinations of antibody therapeutics.

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[5]
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[6]
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[7]
Progress and prospect of ASCT combined with CAR-T therapy in the treatment of multiple myeloma.

Ther Adv Hematol. 2024-3-13

[8]
A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.

J Pharmacokinet Pharmacodyn. 2023-6

本文引用的文献

[1]
Natural Killer Cells in Immunotherapy: Are We Nearly There?

Cancers (Basel). 2020-10-27

[2]
Clinical development of CAR T cell therapy in China: 2020 update.

Cell Mol Immunol. 2021-4

[3]
Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies.

Front Immunol. 2020

[4]
Recent advances in CAR-T cell engineering.

J Hematol Oncol. 2020-7-2

[5]
CAR-T Cell Therapy in Cancer: Tribulations and Road Ahead.

J Immunol Res. 2020

[6]
CAR T-Cells.

Adv Exp Med Biol. 2020

[7]
CAR-T treatment for hematological malignancies.

J Investig Med. 2020-6

[8]
Engineering strategies to overcome the current roadblocks in CAR T cell therapy.

Nat Rev Clin Oncol. 2019-12-17

[9]
Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.

Front Oncol. 2019-11-21

[10]
CAR-T Cells: Future Perspectives.

Hemasphere. 2019-3-19

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