Intradermal Vaccinations With RNA Coding for TAA Generate CD8+ and CD4+ Immune Responses and Induce Clinical Benefit in Vaccinated Patients
Open accessAbstract
The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 µg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0-3, 7-10, 28, and 42 (50 µg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4(+) and CD8(+) T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.
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Those studies showed RNA vaccines to be well tolerated and immunogenic.
“Those studies showed RNA vaccines to be well tolerated and immunogenic.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [37]
Various RNA vaccines have been evaluated in human clinical trials, including naked and formulated non-amplifying mRNA and self-amplifying RNA packaged in VRPs.
“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 [37]
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References 43 · Cited by 226
- Authors
- Rittig, S. M., Haentschel, M., Weimer, K. J., Heine, A., Muller, M. R., Brugger, W., Horger, M. S., Maksimovic, O., Stenzl, A., Hoerr, I., Rammensee, H.-G., Holderried, T. A., Kanz, L., Pascolo, S., & Brossart, P.
- Affiliations
- University of Tübingen (DE)
- University of Bonn (DE)
- CureVac (Germany) (DE)
- University of Zurich (CH)
- Corresponding author
- Brossart, Peter
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 19
- Issue
- 5
- Pages
- 990-999
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3098631
- OpenAlex
- W1971201276
- Cited by
- 226
- References
- 43
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 13 · 2022: 21 · 2021: 29 · 2020: 14 · 2019: 13 · 2018: 6 · 2017: 12 · 2016: 15 · 2015: 18 · 2014: 16 · 2013: 27 · 2012: 12
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biotechnology › Cancer Research and Treatments
- Keywords
- mRNA vaccination, intradermal vaccination, renal cell carcinoma, stage IV renal cell carcinoma, tumor-associated antigens, GM-CSF adjuvant, MUC1, carcinoembryonic antigen, HER2/neu, telomerase, survivin, MAGE-1, CD8+ T cell responses, CD4+ T cell responses, interferon-gamma, vaccine safety, vaccine immunogenicity, survival
- MeSH terms
- Adjuvants, Immunologic, Aged, Antigens, Neoplasm, Carcinoma, Renal Cell, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, RNA, Messenger, Genetic Therapy, CD4-Positive T-Lymphocytes, Granulocyte-Macrophage Colony-Stimulating Factor, CD8-Positive T-Lymphocytes, Cancer Vaccines
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