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

by Oehm, Petra , Michel, Kristina , Weber, David , Mroz, Karolina , Hayduk, Nina , Suchan, Martin , Wöll, Stefan , Ouchan, Yasmina , Jahndel, Veronika , Kühlcke, Klaus , Billmeier, Arne , Sahin, Ugur , Birtel, Matthias , Bukur, Thomas , Hobohm, Kathleen , Türeci, Özlem , Klein, Oliver , Christ, Elmar , Diken, Mustafa , Rengstl, Benjamin , Reinhard, Katharina , Kuna, Kathrin , Kranz, Lena

in Animals / Antigen-presenting cells / Antigens / Cancer Vaccines - therapeutic use / Chimeric antigen receptors / Claudins - antagonists & inhibitors / Claudins - immunology / Effectiveness / Female / Gene expression / Humans / Immunotherapy, Adoptive - methods / Lymphocytes / Lymphocytes T / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Motor Vehicles / mRNA vaccines / Proteins / Receptors / Receptors, Chimeric Antigen - immunology / Ribonucleic acid / RNA / RNA - therapeutic use / Solid tumors / Stimulation / T-Lymphocytes - immunology / T-Lymphocytes - transplantation / Tumors / Vaccines / Vaccines, Synthetic - therapeutic use

2020

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

2020

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2020

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Journal Article

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

Oehm, Petra,

Michel, Kristina,

Weber, David,

Mroz, Karolina,

Hayduk, Nina,

Suchan, Martin,

Wöll, Stefan,

Ouchan, Yasmina,

Jahndel, Veronika,

Kühlcke, Klaus,

Billmeier, Arne,

Sahin, Ugur,

Birtel, Matthias,

Bukur, Thomas,

Hobohm, Kathleen,

Türeci, Özlem,

Klein, Oliver,

Christ, Elmar,

Diken, Mustafa,

Rengstl, Benjamin,

Reinhard, Katharina,

Kuna, Kathrin,

Kranz, Lena

2020

Overview

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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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

Animals

/ Antigen-presenting cells

/ Antigens

/ Cancer Vaccines - therapeutic use

/ Chimeric antigen receptors

/ Claudins - antagonists & inhibitors

/ Claudins - immunology