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Science. 2020 Jan 2. pii: eaay5967. doi: 10.1126/science.aay5967. [Epub ahead of print]

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

Author information

1
Biopharmaceutical New Technologies (BioNTech) Corporation, BioNTech Cell & Gene Therapies GmbH, BioNTech Innovative Manufacturing Services GmbH, An der Goldgrube 12, 55131 Mainz, Germany.
2
TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University GmbH, Freiligrathstr. 12, 55131 Mainz, Germany.
3
Biopharmaceutical New Technologies (BioNTech) Corporation, BioNTech Cell & Gene Therapies GmbH, BioNTech Innovative Manufacturing Services GmbH, An der Goldgrube 12, 55131 Mainz, Germany. ugur.sahin@biontech.de.

Abstract

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 non-persistence 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 dendritic 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 sub-therapeutic CAR-T cell doses.

PMID:
31896660
DOI:
10.1126/science.aay5967

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