PT  - JOURNAL ARTICLE
AU  - Reinhard, Katharina
AU  - Rengstl, Benjamin
AU  - Oehm, Petra
AU  - Michel, Kristina
AU  - Billmeier, Arne
AU  - Hayduk, Nina
AU  - Klein, Oliver
AU  - Kuna, Kathrin
AU  - Ouchan, Yasmina
AU  - Wöll, Stefan
AU  - Christ, Elmar
AU  - Weber, David
AU  - Suchan, Martin
AU  - Bukur, Thomas
AU  - Birtel, Matthias
AU  - Jahndel, Veronika
AU  - Mroz, Karolina
AU  - Hobohm, Kathleen
AU  - Kranz, Lena
AU  - Diken, Mustafa
AU  - Kühlcke, Klaus
AU  - Türeci, Özlem
AU  - Sahin, Ugur
TI  - An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors
AID  - 10.1126/science.aay5967
DP  - 2020 Jan 24
TA  - Science
PG  - 446--453
VI  - 367
IP  - 6476
4099  - http://science.sciencemag.org/content/367/6476/446.short
4100  - http://science.sciencemag.org/content/367/6476/446.full
SO  - Science2020 Jan 24; 367
AB  - Chimeric antigen receptor (CAR)–T cells have been clinically effective in killing certain hematological malignancies, but achieving long-term patient responses for solid tumors remains a challenge. Reinhard et al. describe a two-part “CARVac” strategy to overcome poor CAR-T cell stimulation and responses in vivo. They introduce the tight junction protein claudin 6 (CLDN6) as a new CAR-T cell target and designed a nanoparticulate RNA vaccine encoding a chimeric receptor directed toward CLDN6. This lipoplex RNA vaccine promotes CLDN6 expression on the surface of dendritic cells, which in turn stimulates and enhances the efficacy of CLDN6-CAR-T cells for improved tumor therapy.Science, this issue p. 446Chimeric 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.