气候变化领域集成服务门户(CCPortal): An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors

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DOI	10.1126/science.aay5967
	An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors
	Reinhard K.; Rengstl B.; Oehm P.; Michel K.; Billmeier A.; Hayduk N.; Klein O.; Kuna K.; Ouchan Y.; Wöll S.; Christ E.; Weber D.; Suchan M.; Bukur T.; Birtel M.; Jahndel V.; Mroz K.; Hobohm K.; Kranz L.; Diken M.; Kühlcke K.; Türeci Ö.; Sahin U.
发表日期	2020
ISSN	0036-8075
起始页码	446
结束页码	453
卷号	367 期号:6476
英文摘要	Chimeric antigen receptor (CAR)–T cells have shown efficacy in patients with B cell malignancies. Yet, their application for solid tumors has challenges that include limited cancer-specific targets and nonpersistence of adoptively transferred CAR-T cells. Here, we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a CAR target in solid tumors and a strategy to overcome inefficient CAR-T cell stimulation in vivo. We demonstrate that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulates adoptively transferred CAR-T cells. Presentation of the natively folded target on resident antigen-presenting cells promotes cognate and selective expansion of CAR-T cells. Improved engraftment of CAR-T cells and regression of large tumors in difficult-to-treat mouse models was achieved at subtherapeutic CAR-T cell doses. Copyright © 2020 The Authors,
关键词	chimeric antigen receptor claudin 6 RNA vaccine antigen cell component protein RNA tumor vaccine animal cell animal experiment animal model animal tissue antigen presenting cell antineoplastic activity Article cell stimulation cell transport chimeric antigen receptor T-cell immunotherapy controlled study drug efficacy human human cell in vivo study mouse nonhuman phenotype priority journal real time polymerase chain reaction solid malignant neoplasm therapy effect vaccination coverage
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133762
推荐引用方式 GB/T 7714	Reinhard K.,Rengstl B.,Oehm P.,et al. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors[J]. Science,2020,367(6476).
APA	Reinhard K..,Rengstl B..,Oehm P..,Michel K..,Billmeier A..,...&Sahin U..(2020).An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors.,367(6476).
MLA	Reinhard K.,et al."An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors".367.6476(2020).