重定向至 B7-H3 的 CAR T 细胞治疗小儿实体瘤:现状与未来展望

Rebecca Epperly, Stephen Gottschalk, Christopher DeRenzo
{"title":"重定向至 B7-H3 的 CAR T 细胞治疗小儿实体瘤:现状与未来展望","authors":"Rebecca Epperly,&nbsp;Stephen Gottschalk,&nbsp;Christopher DeRenzo","doi":"10.1016/j.ejcped.2024.100160","DOIUrl":null,"url":null,"abstract":"<div><p>Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an alternative to conventional treatment options but require the identification of differentially expressed antigens to direct antitumor activity to sites of disease. B7-H3 (CD276) is an immune regulatory protein that is expressed in a range of malignancies and has limited expression in normal tissues. B7-H3 is highly expressed in pediatric solid tumors including osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma, and many rare tumors. In this article we review B7-H3-targeted chimeric antigen receptor (B7-H3-CAR) T cell therapies for pediatric solid tumors, reporting preclinical development strategies and outlining the landscape of active pediatric clinical trials. We identify challenges to the success of CAR T cell therapy for solid tumors including localizing to and penetrating solid tumor sites, evading the hostile tumor microenvironment, supporting T cell expansion and persistence, and avoiding intrinsic tumor resistance. We highlight strategies to overcome these challenges and enhance the effect of B7-H3-CAR T cells, including advanced CAR T cell design and incorporation of combination therapies.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000199/pdfft?md5=c747012f8719471c331ca17f416f2eef&pid=1-s2.0-S2772610X24000199-main.pdf","citationCount":"0","resultStr":"{\"title\":\"CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives\",\"authors\":\"Rebecca Epperly,&nbsp;Stephen Gottschalk,&nbsp;Christopher DeRenzo\",\"doi\":\"10.1016/j.ejcped.2024.100160\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an alternative to conventional treatment options but require the identification of differentially expressed antigens to direct antitumor activity to sites of disease. B7-H3 (CD276) is an immune regulatory protein that is expressed in a range of malignancies and has limited expression in normal tissues. B7-H3 is highly expressed in pediatric solid tumors including osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma, and many rare tumors. In this article we review B7-H3-targeted chimeric antigen receptor (B7-H3-CAR) T cell therapies for pediatric solid tumors, reporting preclinical development strategies and outlining the landscape of active pediatric clinical trials. We identify challenges to the success of CAR T cell therapy for solid tumors including localizing to and penetrating solid tumor sites, evading the hostile tumor microenvironment, supporting T cell expansion and persistence, and avoiding intrinsic tumor resistance. We highlight strategies to overcome these challenges and enhance the effect of B7-H3-CAR T cells, including advanced CAR T cell design and incorporation of combination therapies.</p></div>\",\"PeriodicalId\":94314,\"journal\":{\"name\":\"EJC paediatric oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2772610X24000199/pdfft?md5=c747012f8719471c331ca17f416f2eef&pid=1-s2.0-S2772610X24000199-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJC paediatric oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2772610X24000199\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJC paediatric oncology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772610X24000199","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

尽管采用了强化疗法,但复发或难治性实体瘤儿科患者的治疗效果不佳,需要新的治疗方法。免疫疗法为传统治疗方案提供了另一种选择,但需要识别不同表达的抗原,将抗肿瘤活性引导到疾病部位。B7-H3(CD276)是一种免疫调节蛋白,在多种恶性肿瘤中表达,在正常组织中表达有限。B7-H3在小儿实体瘤中高度表达,包括骨肉瘤、横纹肌肉瘤、尤文肉瘤、Wilms瘤、神经母细胞瘤和许多罕见肿瘤。在这篇文章中,我们回顾了针对小儿实体瘤的B7-H3靶向嵌合抗原受体(B7-H3-CAR)T细胞疗法,报告了临床前开发策略,并概述了活跃的小儿临床试验情况。我们指出了CAR T细胞疗法成功治疗实体瘤所面临的挑战,包括定位和穿透实体瘤部位、避开恶劣的肿瘤微环境、支持T细胞扩增和持久性以及避免内在肿瘤耐药性。我们重点介绍了克服这些挑战并增强 B7-H3-CAR T 细胞疗效的策略,包括先进的 CAR T 细胞设计和联合疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives

Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an alternative to conventional treatment options but require the identification of differentially expressed antigens to direct antitumor activity to sites of disease. B7-H3 (CD276) is an immune regulatory protein that is expressed in a range of malignancies and has limited expression in normal tissues. B7-H3 is highly expressed in pediatric solid tumors including osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma, and many rare tumors. In this article we review B7-H3-targeted chimeric antigen receptor (B7-H3-CAR) T cell therapies for pediatric solid tumors, reporting preclinical development strategies and outlining the landscape of active pediatric clinical trials. We identify challenges to the success of CAR T cell therapy for solid tumors including localizing to and penetrating solid tumor sites, evading the hostile tumor microenvironment, supporting T cell expansion and persistence, and avoiding intrinsic tumor resistance. We highlight strategies to overcome these challenges and enhance the effect of B7-H3-CAR T cells, including advanced CAR T cell design and incorporation of combination therapies.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
0.20
自引率
0.00%
发文量
0
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信