AccScience Publishing / GPD / Volume 1 / Issue 1 / DOI: 10.36922/gpd.v1i1.114
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REVIEW

Gene-modified T cell therapy for cancer: Current challenges and potential solutions

Xinfeng Chen1,2† Shasha Liu1,2† Zhen Zhang1,2 Yi Zhang1,2,3,4*
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1 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
2 Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
3 School of Life Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China
4 Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, 450052, Henan, China
Submitted: 29 May 2022 | Accepted: 14 June 2022 | Published: 28 June 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Immunotherapy has achieved significant breakthroughs in patients with hematological diseases and various cancers. The adoptive transfer of T cells, especially gene-modified T cells such as chimeric antigen receptor T (CAR-T) cells and T cell receptor-engineered T (TCR-T) cells, is developing rapidly. Since 2017, eight CAR-T cell products have been approved for the treatment of hematological diseases, such as refractory or relapsed acute B lymphoblastic leukemia, specific subtypes of B cell lymphoma, and multiple myeloma. The first TCR-T cell product, Kimmtrak, was approved for the treatment of unresectable or metastatic uveal melanoma in March 2022. However, there are still many problems, including side effects, relapse, high demand for individualization, and expensive cost in hematological diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability, immunosuppressive microenvironment, and low response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, many novel strategies for improving the anti-tumor effect and safety of gene-modified T cell immunotherapy have been attempted. This paper presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy, focusing on applications, clinical trials, problems, and potential solutions.

Keywords
Immunotherapy
Chimeric antigen receptor T cell
T cell receptor-engineered T cell
Tumor microenvironment
Solid tumor
Funding
Healthy Talents Project of Henan Province
National Natural Science Foundation of China
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Conflict of interest
The authors declare that they have no competing interests.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing