The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA
Abstract
Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models. Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits. The active pharmaceutical ingredient in such vaccines can be DNA, RNA, protein, or peptide and can be administered naked, encapsulated, or after delivery in vitro into cells that are then adoptively transferred. One of the easiest, most versatile and theoretically safest technologies relies on the direct injection of naked messenger RNA (mRNA) that code for tumor antigens. We and others have shown in mice that intradermal application of naked mRNA results in protein expression and the development of an immune response. We used this protocol to vaccinate 15 melanoma patients. For each patient a growing metastasis was removed, total RNA was extracted, reverse-transcribed, amplified, and cloned. Libraries of cDNA were transcribed to produce unlimited amounts of copy mRNA. Autologous preparations were applied intradermally in combination with granulocyte macrophage colony-stimulating factor as adjuvant. We demonstrate here that such treatment is feasible and safe (phase 1 criteria). Furthermore, an increase in antitumor humoral immune response was seen in some patients. However, a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials.
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“Those studies showed RNA vaccines to be well tolerated and immunogenic.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [38]
In the citing paper
“Various RNA vaccines have been evaluated in human clinical trials, including naked and formulated non-amplifying mRNA (37-39) and self-amplifying RNA packaged in VRPs (25).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [38]
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The clinical progress of mRNA vaccines and immunotherapies
Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R., & Anderson, D. G. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01294-2 · Cited by 823
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 852
Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy
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Metadata
- Authors
- Weide, B., Carralot, J.-P., Reese, A., Scheel, B., Eigentler, T. K., Hoerr, I., Rammensee, H.-G., Garbe, C., & Pascolo, S.
- Affiliations
- University of Tübingen (DE)
- CureVac (Germany) (DE)
- Corresponding author
- Weide, Benjamin
- Reese, Anne
- Eigentler, Thomas Kurt
- Garbe, Claus
- Venue
- Journal of Immunotherapy
- Published
- 2008-02
- Volume
- 31
- Issue
- 2
- Pages
- 180-188
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W2066847748
- Cited by
- 261
- References
- 15
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 17 · 2023: 26 · 2022: 22 · 2021: 30 · 2020: 13 · 2019: 12 · 2018: 8 · 2017: 11 · 2016: 16 · 2015: 13 · 2014: 12 · 2013: 14 · 2012: 13
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- mRNA vaccination, cancer immunotherapy, melanoma, tumor antigens, intradermal injection, GM-CSF, adjuvants, humoral immune response, feasibility and safety
- MeSH terms
- Adult, Aged, Antibody Formation, Antigens, Neoplasm, Female, Humans, Immunity, Cellular, Injections, Intradermal, Interferon-gamma, Male, Melanoma, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, RNA, Messenger, Monitoring, Immunologic, CD4-Positive T-Lymphocytes, Granulocyte-Macrophage Colony-Stimulating Factor, Treatment Outcome, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cell Line, Tumor
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