An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors

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Science  24 Jan 2020:
Vol. 367, Issue 6476, pp. 446-453
DOI: 10.1126/science.aay5967

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A one-two, CAR-T cell punch

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. 446

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