Page 32 - GPD-1-1

Gene & Protein in Disease

REVIEW ARTICLE
Gene-modified T cell therapy for cancer: Current

challenges and potential solutions

1,2
Xinfeng Chen 1,2† , Shasha Liu 1,2† , Zhen Zhang , and Yi Zhang 1,2,3,4 *
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

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,
† These authors contributed equally relapse, high demand for individualization, and expensive cost in hematological
to this work. diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability,
*Corresponding author: immunosuppressive microenvironment, and low response in solid tumors. With
Yi Zhang the in-depth exploration of tumor immunology and the development of genetic
(yizhang@zzu.edu.cn) engineering technology, many novel strategies for improving the anti-tumor effect
Citation: Chen X, Liu S, Zhang Z, and safety of gene-modified T cell immunotherapy have been attempted. This paper
et al. Gene-modified T cell therapy presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy,
for cancer: Current challenges and
potential solutions. Gene Protein focusing on applications, clinical trials, problems, and potential solutions.
Dis, 1(1): 114.
https://doi.org/10.36922/gpd.v1i1.114
Keywords: Immunotherapy; Chimeric antigen receptor T cell; T cell receptor-engineered
Received: May 29, 2022
Accepted: June 14, 2022 T cell; Tumor microenvironment; Solid tumor
Published Online: June 28, 2022
Copyright: © 2022 Author(s).
This is an Open Access article
distributed under the terms of the 1. Introduction
Creative Commons Attribution
License, permitting distribution, In recent years, chimeric antigen receptor T (CAR-T) cell therapy has become one
and reproduction in any medium, of the most promising therapeutic methods in cancer immunotherapy because of
provided the original work is
properly cited. the remarkably effective and durable immune response it produces in hematological
Publisher’s Note: AccScience malignancies [1,2] . CD19 and B cell maturation antigen (BCMA) CAR-T cell products
[3]
Publishing remains neutral with have been approved for clinical applications worldwide . This has promoted further
regard to jurisdictional claims in
published maps and institutional large-scale clinical trials of CAR-T cells in other malignant diseases. However, CAR-T
affiliations. cell therapy is afflicted with several problems, such as toxicity, resistance or relapse, and

Volume 1 Issue 1 (2022) 1 https://doi.org/10.36922/gpd.v1i1.114