{"title":"CAR T-cell therapy for B-cell lymphomas: outcomes and resistance mechanisms.","authors":"Tyce J Kearl, Fateeha Furqan, Nirav N Shah","doi":"10.1007/s10555-024-10228-0","DOIUrl":null,"url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells are an exciting curative intent approach to the treatment of non-Hodgkin lymphomas (NHLs). Several products have received FDA approval for 2nd or 3rd line indications, and studies are underway for their use earlier in the disease course. These CAR T cells are ex vivo manufactured autologous cell products that specifically target tumor antigens to optimize tumor specificity and minimize off-tumor side effects-in NHLs, this is typically achieved by targeting B-cell antigens. Engagement of the CAR and corresponding antigen is designed to result in T-cell activation and subsequent tumor clearance. While curative for many NHL patients, too many patients fail to respond to or relapse following CAR T-cell treatment, and salvage options post CAR T-cell therapy are limited. Treatment failures occur because of myriad resistance mechanisms including CAR T-cell dysfunction, generalized immune dysregulation, and intrinsic tumor resistance. Focusing on patients with NHL, we review the clinical outcomes of CAR T-cell therapy and the major resistance mechanisms that lead to poor outcomes. We also review the many innovative and encouraging strategies that are being developed to improve CAR T-cell therapy for NHL.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"12"},"PeriodicalIF":7.7000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer and Metastasis Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10555-024-10228-0","RegionNum":2,"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 cells are an exciting curative intent approach to the treatment of non-Hodgkin lymphomas (NHLs). Several products have received FDA approval for 2nd or 3rd line indications, and studies are underway for their use earlier in the disease course. These CAR T cells are ex vivo manufactured autologous cell products that specifically target tumor antigens to optimize tumor specificity and minimize off-tumor side effects-in NHLs, this is typically achieved by targeting B-cell antigens. Engagement of the CAR and corresponding antigen is designed to result in T-cell activation and subsequent tumor clearance. While curative for many NHL patients, too many patients fail to respond to or relapse following CAR T-cell treatment, and salvage options post CAR T-cell therapy are limited. Treatment failures occur because of myriad resistance mechanisms including CAR T-cell dysfunction, generalized immune dysregulation, and intrinsic tumor resistance. Focusing on patients with NHL, we review the clinical outcomes of CAR T-cell therapy and the major resistance mechanisms that lead to poor outcomes. We also review the many innovative and encouraging strategies that are being developed to improve CAR T-cell therapy for NHL.
期刊介绍:
Contemporary biomedical research is on the threshold of an era in which physiological and pathological processes can be analyzed in increasingly precise and mechanistic terms.The transformation of biology from a largely descriptive, phenomenological discipline to one in which the regulatory principles can be understood and manipulated with predictability brings a new dimension to the study of cancer and the search for effective therapeutic modalities for this disease. Cancer and Metastasis Reviews provides a forum for critical review and discussion of these challenging developments.
A major function of the journal is to review some of the more important and interesting recent developments in the biology and treatment of malignant disease, as well as to highlight new and promising directions, be they technological or conceptual. Contributors are encouraged to review their personal work and be speculative.