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

Science. 2020 Jan 24;367(6476):446-453. doi: 10.1126/science.aay5967. Epub 2020 Jan 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / therapeutic use*
  • Claudins / antagonists & inhibitors*
  • Claudins / immunology
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RNA / therapeutic use
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Vaccines, Synthetic / therapeutic use


  • Cancer Vaccines
  • Claudins
  • Receptors, Chimeric Antigen
  • Vaccines, Synthetic
  • RNA
  • claudin 6