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

Author:

Reinhard Katharina1ORCID,Rengstl Benjamin1ORCID,Oehm Petra1ORCID,Michel Kristina1,Billmeier Arne1ORCID,Hayduk Nina1,Klein Oliver1,Kuna Kathrin1,Ouchan Yasmina1,Wöll Stefan1,Christ Elmar1,Weber David2,Suchan Martin2,Bukur Thomas2ORCID,Birtel Matthias1,Jahndel Veronika1,Mroz Karolina1,Hobohm Kathleen1,Kranz Lena1,Diken Mustafa2,Kühlcke Klaus1,Türeci Özlem1ORCID,Sahin Ugur123ORCID

Affiliation:

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 gGmbH, Freiligrathstr. 12, 55131 Mainz, Germany.

3. Helmholtz Institute for Translational Oncology Mainz, HI-TRON Mainz, Obere Zahlbacher Str. 63, 55131 Mainz, Germany.

Abstract

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

Funder

German Federal Ministry of Education and Research

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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