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

Sahin, Ugur, Derhovanessian, Evelyna, Miller, Matthias, Kloke, Björn-Philipp, Simon, Petra, Löwer, Martin, Bukur, Valesca, Tadmor, Arbel D., Luxemburger, Ulrich, Schrörs, Barbara, Omokoko, Tana, Vormehr, Mathias, Albrecht, Christian, Paruzynski, Anna, Kuhn, Andreas N., Buck, Janina, Heesch, Sandra, Schreeb, Katharina H., Müller, Felicitas, Ortseifer, Inga, Vogler, Isabel, Godehardt, Eva, Attig, Sebastian, Rae, Richard, Breitkreuz, Andrea, Tolliver, Claudia, Suchan, Martin, Martic, Goran, Hohberger, Alexander, Sorn, Patrick, Diekmann, Jan, Ciesla, Janko, Waksmann, Olga, Brück, Alexandra-Kemmer, Witt, Meike, Zillgen, Martina, Rothermel, Andree, Kasemann, Barbara, Langer, David, Bolte, Stefanie, Diken, Mustafa, Kreiter, Sebastian, Nemecek, Romina, Gebhardt, Christoffer, Grabbe, Stephan, Höller, Christoph, Utikal, Jochen, Huber, Christoph, Loquai, Carmen, Türeci, Özlem·2017·Nature

DOI 10.1038/nature23003

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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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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)
ORCID: Miller, Matthias
Tadmor, Arbel D.
Luxemburger, Ulrich
Schrörs, Barbara
Vormehr, Mathias
Albrecht, Christian
Kuhn, Andreas N.
Schreeb, Katharina H.
Vogler, Isabel
Suchan, Martin
Sorn, Patrick
Diken, Mustafa
Kreiter, Sebastian
Gebhardt, Christoffer
Grabbe, Stephan
Utikal, Jochen
Loquai, Carmen
Türeci, Özlem
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-07-05
Volume: 547
Issue: 7662
Pages: 222-226
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature23003
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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