Unlocking T cell exhaustion:Insights and implications for CAR-T cell therapy

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外文摘要：Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell ther-apies targeting CD19 or B cell maturation antigen(BCMA)for hematological malignancies,albeit with moderate outcomes in solid tumors.However,despite these advancements,the efficacy of CAR-T therapy is often compromised by T cell exhaustion,a phenomenon that impedes the persistence and effector func-tion of CAR-T cells,leading to a relapse rate of up to 75％in patients treated with CD 19 orCD22 CAR-T cells for hematological malignancies.Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies.In this review,we provide a compre-hensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy.These insights,combined with lessons learned from benchmarking CAR-T based products in recent clinical trials,aim to address the challenges posed by T cell exhaustion,potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.

外文关键词：

Cancer immunotherapyCAR-T therapyT cell exhaustionTumor immune microenvironmentSpatial immune contextureSingle-cell technologiesCAR-T engineeringCombination therapy

作者：

Dian Xiong、Haijun Yu、Zhi-Jun Sun

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作者单位：

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School & Hospital of Stomatology,Frontier Science Center for Immunology and Metabolism,Taikang Center for Life and Medical Science,Wuhan University,Wuhan 430079,China

Department of Radiation and Medical Oncology,Hubei Province Cancer Clinical Study Center,Hubei Key Laboratory of Tumor Biological Behaviors,Zhongnan Hospital of Wuhan University,Wuhan 430071,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program,ChinaFundamental Research Funds for the Central Universities,ChinaInterdisciplinary Innovative Foundation of Wuhan University,China

项目编号：

8227320282072996820733492022YFC25042002042024kf0021XNJC202303

出版年：

2024

DOI：

10.1016/j.apsb.2024.04.022

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(8)