嵌合抗原受体
过继性细胞移植
抗原
生物
T细胞
免疫学
癌症研究
免疫系统
作者
Katharina Reinhard,Benjamin Rengstl,Petra Oehm,Kristina Michel,Arne Billmeier,Nina Hayduk,Oliver Klein,Kathrin Kuna,Yasmina Ouchan,Stefan Wöll,Elmar Christ,D. F. Weber,M Suchan,Thomas Bukur,Matthias Birtel,Veronika Jahndel,Karolina Mroz,Kathleen Hobohm,Lena M. Kranz,Mustafa Diken,Klaus Kühlcke,Özlem Türeci,Uğur Şahin
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2020-01-24
卷期号:367 (6476): 446-453
被引量:270
标识
DOI:10.1126/science.aay5967
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.
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