Cited by 2,488Immunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkersvaccines and immunoinformatics approaches

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer

Abstract

T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of β2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.

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Crossref · 10.1038/nature23003

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Metadata

Authors
Sahin, U., Derhovanessian, E., Miller, M., Kloke, B.-P., Simon, P., Löwer, M., Bukur, V., Tadmor, A. D., Luxemburger, U., Schrörs, B., Omokoko, T., Vormehr, M., Albrecht, C., Paruzynski, A., Kuhn, A. N., Buck, J., Heesch, S., Schreeb, K. H., Müller, F., Ortseifer, I., Vogler, I., Godehardt, E., Attig, S., Rae, R., Breitkreuz, A., Tolliver, C., Suchan, M., Martic, G., Hohberger, A., Sorn, P., Diekmann, J., Ciesla, J., Waksmann, O., Brück, A.-K., Witt, M., Zillgen, M., Rothermel, A., Kasemann, B., Langer, D., Bolte, S., Diken, M., Kreiter, S., Nemecek, R., Gebhardt, C., Grabbe, S., Höller, C., Utikal, J., Huber, C., Loquai, C., & Türeci, Ö.
Affiliations
  • BioNTech (Germany) (DE)
  • Johannes Gutenberg University Mainz (DE)
  • University Medical Center of the Johannes Gutenberg University Mainz (DE)
  • Medical University of Vienna (AT)
  • German Cancer Research Center (DE)
Venue
Nature
Published
2017-07-05
Volume
547
Issue
7662
Pages
222-226
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2724264513
Cited by
2,488
References
43
Citations by year
2026: 228 · 2025: 255 · 2024: 259 · 2023: 299 · 2022: 277 · 2021: 317 · 2020: 290 · 2019: 262 · 2018: 239 · 2017: 58
FWCI
105.75
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (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 › vaccines and immunoinformatics approaches
Keywords
neoantigens, melanoma, cancer immunotherapy, T cell response, metastasis prevention, anti-PD-1 therapy, acquired resistance, beta2-microglobulin deficiency, vaccine safety and tolerability, tumor cell killing, tumor-infiltrating T cells
MeSH terms
Nivolumab, Antibodies, Monoclonal, Epitopes, beta 2-Microglobulin, Humans, Immunotherapy, Melanoma, Mutation, Neoplasm Metastasis, Neoplasm Recurrence, Local, RNA, T-Lymphocytes, Vaccination, CD8 Antigens, Cancer Vaccines, Precision Medicine, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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