{"title":"The mechanisms and countermeasures for CAR-T cell expansion and persistence deficiency","authors":"Yu-Tong Bao , Meng Lv , Xiao-Jun Huang , Xiang-Yu Zhao","doi":"10.1016/j.canlet.2025.217771","DOIUrl":null,"url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological malignancies, particularly B-cell malignancies. However, its high risk of relapse and low efficacy in malignancies such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have limited its clinical utility. The expansion, infiltration and persistence of CAR-T cells are key determinants of their efficacy. It has been recognized that limited expansion and lack of persistence are major contributors to non-remission and early relapse, highlighting the need to elucidate their mechanisms and countermeasures. In this review, we described features of CAR-T cell expansion and persistence in various hematogenic malignancies and solid tumors. Then, current knowledge on the mechanisms underlying deficiency in CAR-T cell expansion and persistence is presented, focusing on the intrinsic deficiency of CAR-T cells as well as their interaction with the systemic and local immune environment. Finally, we summarize approaches to enhance CAR-T cell expansion and persistence by improving CAR-T cell quality and overcoming the immunosuppressive environment.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"626 ","pages":"Article 217771"},"PeriodicalIF":9.1000,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304383525003374","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological malignancies, particularly B-cell malignancies. However, its high risk of relapse and low efficacy in malignancies such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have limited its clinical utility. The expansion, infiltration and persistence of CAR-T cells are key determinants of their efficacy. It has been recognized that limited expansion and lack of persistence are major contributors to non-remission and early relapse, highlighting the need to elucidate their mechanisms and countermeasures. In this review, we described features of CAR-T cell expansion and persistence in various hematogenic malignancies and solid tumors. Then, current knowledge on the mechanisms underlying deficiency in CAR-T cell expansion and persistence is presented, focusing on the intrinsic deficiency of CAR-T cells as well as their interaction with the systemic and local immune environment. Finally, we summarize approaches to enhance CAR-T cell expansion and persistence by improving CAR-T cell quality and overcoming the immunosuppressive environment.
期刊介绍:
Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research.
Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy.
By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.