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Intranodal Vaccination with Naked Antigen-Encoding RNA Elicits Potent Prophylactic and Therapeutic Antitumoral Immunity
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Abstract
Although naked antigen-encoding RNA has entered clinical testing, basic knowledge on how to apply this promising novel vaccine format is still pending. By comparing different administration routes, we observed surprisingly potent antigen-specific T-cell immunity upon intranodal injection of naked antigen-encoding RNA. RNA was selectively uptaken by resident dendritic cells, propagated a T-cell attracting and stimulatory intralymphatic milieu, and led to efficient expansion of antigen-specific CD8+ as well as CD4+ T cells. By intranodal treatment of mice with repeated cycles of RNA, we achieved de novo priming of naïve T cells, which became potent cytolytic effectors capable of homing to primary and secondary lymphatic tissues as well as memory T cells. In tumor-bearing mice intralymphatic RNA vaccination elicited protective and therapeutic antitumor immune responses, resulting in a remarkable survival benefit as compared with other treatment regimens. This is the first report of strong systemic antigen-specific Th1-type immunity and cancer cure achieved with naked antigen-encoding RNA in preclinical animal models. Cancer Res; 70(22); 9031–40. ©2010 AACR.
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“In addition, it has been previously demonstrated that mRNA represents a potent vaccine technology (Kreiter et al, 2010; Fotin‐Mleczek et al, 2011).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Kreiter et al, 2010
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Metadata
- Authors
- Kreiter, S., Selmi, A., Diken, M., Koslowski, M., Britten, C. M., Huber, C., Türeci, Ö., & Sahin, U.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Authors' Affiliations: 1Center for Translational Oncology and Immunology (TRON), 2Ribological, Biontech AG, and 3Department of Internal Medicine III, Division of Translational and Experimental Oncology, Johannes Gutenberg University, Mainz, Germany
- Venue
- Cancer Research
- Published
- 2010-11-14
- Volume
- 70
- Issue
- 22
- Pages
- 9031-9040
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2125677437
- Cited by
- 309
- References
- 34
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 25 · 2023: 30 · 2022: 21 · 2021: 22 · 2020: 23 · 2019: 13 · 2018: 17 · 2017: 20 · 2016: 19 · 2015: 23 · 2014: 21 · 2013: 22 · 2012: 13
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- intranodal injection, dendritic cells, CD8+ T cells, CD4+ T cells, Th1 response, antitumor immunity, prophylactic and therapeutic vaccination, T cell homing, memory T cells, cancer immunotherapy
- MeSH terms
- Animals, Antigens, Cytotoxicity, Immunologic, Dendritic Cells, Flow Cytometry, Immunization, Lymph Nodes, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Experimental, RNA, CD4-Positive T-Lymphocytes, Survival Analysis, Mice, Knockout, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cell Line, Tumor, Cell Proliferation, Mice
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