Multispecific CAR T Cells Deprive Lymphomas of Escape via Antigen Loss.

IF 15.1 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Annual review of medicine Pub Date : 2023-01-27 DOI:10.1146/annurev-med-042921-024719
Fateeha Furqan, Nirav N Shah
{"title":"Multispecific CAR T Cells Deprive Lymphomas of Escape via Antigen Loss.","authors":"Fateeha Furqan,&nbsp;Nirav N Shah","doi":"10.1146/annurev-med-042921-024719","DOIUrl":null,"url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) modified T cell therapy has transformed the management of relapsed/refractory B cell malignancies. Despite high overall response rates, relapse post CAR T treatment remains a clinical challenge. Loss of target antigen, specifically CD19, is one well-defined mechanism of disease relapse. The mechanism of CD19 loss and which patients are at higher risk of CD19 loss remain poorly understood. To overcome CD19 loss, CARs targeting multiple antigens are being tested in clinical trials. CD19/20 and CD19/22 bispecific CARs demonstrate cytotoxicity against CD19-negative cells in preclinical studies. These CARs have also shown efficacy, safety, and a relatively low rate of CD19-negative relapse in phase I trials. These small studies suggest that multispecific CAR T cells can deprive lymphomas of escape via antigen loss. However, the selection of an ideal target, the right CAR construct, and whether these multispecific CARs can induce long-term remissions are still under investigation.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"74 ","pages":"279-291"},"PeriodicalIF":15.1000,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-med-042921-024719","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 5

Abstract

Chimeric antigen receptor (CAR) modified T cell therapy has transformed the management of relapsed/refractory B cell malignancies. Despite high overall response rates, relapse post CAR T treatment remains a clinical challenge. Loss of target antigen, specifically CD19, is one well-defined mechanism of disease relapse. The mechanism of CD19 loss and which patients are at higher risk of CD19 loss remain poorly understood. To overcome CD19 loss, CARs targeting multiple antigens are being tested in clinical trials. CD19/20 and CD19/22 bispecific CARs demonstrate cytotoxicity against CD19-negative cells in preclinical studies. These CARs have also shown efficacy, safety, and a relatively low rate of CD19-negative relapse in phase I trials. These small studies suggest that multispecific CAR T cells can deprive lymphomas of escape via antigen loss. However, the selection of an ideal target, the right CAR construct, and whether these multispecific CARs can induce long-term remissions are still under investigation.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
多特异性CAR - T细胞通过抗原丢失阻止淋巴瘤逃逸。
嵌合抗原受体(CAR)修饰的T细胞疗法已经改变了复发/难治性B细胞恶性肿瘤的管理。尽管总体有效率很高,CAR - T治疗后的复发仍然是一个临床挑战。靶抗原,特别是CD19的丢失,是疾病复发的一个明确的机制。CD19丢失的机制以及哪些患者具有更高的CD19丢失风险仍然知之甚少。为了克服CD19的缺失,靶向多种抗原的car正在临床试验中进行测试。CD19/20和CD19/22双特异性car在临床前研究中显示出对cd19阴性细胞的细胞毒性。在I期临床试验中,这些car也显示出了疗效、安全性和相对较低的cd19阴性复发率。这些小型研究表明,多特异性CAR - T细胞可以通过抗原丢失来阻止淋巴瘤的逃逸。然而,理想靶点的选择、正确的CAR结构以及这些多特异性CAR是否能诱导长期缓解仍在研究中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Annual review of medicine
Annual review of medicine 医学-医学:内科
CiteScore
24.90
自引率
0.00%
发文量
58
期刊介绍: The Annual Review of Medicine, which has been published since 1950, focuses on important advancements in diverse areas of medicine. These include AIDS/HIV, cardiology, clinical pharmacology, dermatology, endocrinology/metabolism, gastroenterology, genetics, immunology, infectious disease, neurology, oncology/hematology, pediatrics, psychiatry, pulmonology, reproductive medicine, and surgery. The journal's current volume has transitioned from a gated access model to an open access model through the Annual Reviews' Subscribe to Open program. All articles published in the journal are now available under a CC BY license.
期刊最新文献
Endoscopic Approaches for Managing Small Intestinal Disease. Care Models for Cancer Survivors. Candida auris: Epidemiology and Antifungal Strategy. Application and Expectations for Immune Checkpoint Blockade of LAG3 and TIGIT. New Approaches to Respiratory Syncytial Virus Prevention and Treatment.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1