An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors
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
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The RNA-LPX formulation can be used to deliver mRNA encoding claudin 6 (CLDN6), a target for CAR T cell therapy in solid tumours.
“For example, the RNA-LPX formulation can be used to deliver mRNA encoding claudin 6 (CLDN6), a target for CAR T cell therapy in solid tumours213.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [213]
i.v. injection of a CLDN6 mRNA vaccine resulted in CLDN6 expression on splenic dendritic cells and macrophages, promoting the activation of adoptively transferred CLDN6-CAR T cells and leading to suppression of large tumours in mice at a sub-therapeutic CAR T cell dose.
“i.v. injection of this vaccine resulted in CLDN6 expression on splenic dendritic cells and macrophages213, promoting the activation of adoptively transferred CLDN6-CAR T cells and leading to suppression of large tumours in mice at a sub-therapeutic CAR T cell dose213.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [213]
mRNA vaccines can be applied to overcome insufficient stimulation of chimeric antigen receptor T cells in the therapy of solid tumours.
“mRNA vaccines can further be applied to overcome insufficient stimulation of chimeric antigen receptor (CAR) T cells in the therapy of solid tumours213.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [213]
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- Authors
- Reinhard, K., Rengstl, B., Oehm, P., Michel, K., Billmeier, A., Hayduk, N., Klein, O., Kuna, K., Ouchan, Y., Wöll, S., Christ, E., Weber, D., Suchan, M., Bukur, T., Birtel, M., Jahndel, V., Mroz, K., Hobohm, K., Kranz, L., Diken, M., Kühlcke, K., Türeci, Ö., & Sahin, U.
- Affiliations
- BioNTech (Germany) (DE)
- Johannes Gutenberg University Mainz (DE)
- Biopharmaceutical New Technologies (BioNTech) Corporation, BioNTech Cell & Gene Therapies GmbH, BioNTech Innovative Manufacturing Services GmbH, An der Goldgrube 12, 55131 Mainz, Germany.
- Corresponding author
- Reinhard, Katharina
- Rengstl, Benjamin
- Oehm, Petra
- Türeci, Özlem
- ORCID
- Venue
- Science
- Published
- 2020-01-24
- Volume
- 367
- Issue
- 6476
- Pages
- 446-453
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2998563599
- Cited by
- 512
- References
- 37
- Citations by year
- 2026: 54 · 2025: 86 · 2024: 93 · 2023: 92 · 2022: 87 · 2021: 60 · 2020: 38 · 2015: 1
- FWCI
- 25.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- German Federal Ministry of Education and Research (031A024)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- CLDN6, chimeric antigen receptor T cells, RNA vaccines, solid tumors, tight junction proteins, antigen-presenting cells, CAR-T cell expansion, adoptive T cell therapy, tumor regression
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Female, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, T-Lymphocytes, Vaccines, Synthetic, Immunotherapy, Adoptive, Cancer Vaccines, Mice, Claudins
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