The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies

Frontiers in Immunology

Immunology

Leila Mohamed Khosroshahi¹  Leili Aghebati-Maleki²  Behzad Baradaran²  Ali Aghebati-Maleki³  Amin Daei Sorkhabi⁴  Amirhossein Mardi⁴  Aila Sarkesh⁴ 

[1] Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;Stem Cell Research Center, Tabriz University of Medical Science, Tabriz, Iran;Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran;Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;

关键词: chimeric antigen receptor;    CAR T-cell;    immunotherapy;    solid tumors;    challenges;    clinical trials;   

DOI  :  10.3389/fimmu.2023.1113882

 received in 2022-12-01, accepted in 2023-02-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.

【 授权许可】

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Copyright © 2023 Daei Sorkhabi, Mohamed Khosroshahi, Sarkesh, Mardi, Aghebati-Maleki, Aghebati-Maleki and Baradaran