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

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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.

in: NATURE, Jahrgang 547, Nr. 7662, 13.07.2017, S. 222-226.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sahin, U, Derhovanessian, E, Miller, M, Kloke, B-P, Simon, P, Löwer, M, Bukur, V, Tadmor, AD, Luxemburger, U, Schrörs, B, Omokoko, T, Vormehr, M, Albrecht, C, Paruzynski, A, Kuhn, AN, Buck, J, Heesch, S, Schreeb, KH, 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 2017, 'Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer', NATURE, Jg. 547, Nr. 7662, S. 222-226. https://doi.org/10.1038/nature23003

APA

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., ... Türeci, Ö. (2017). Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. NATURE, 547(7662), 222-226. https://doi.org/10.1038/nature23003

Vancouver

Sahin U, Derhovanessian E, Miller M, Kloke B-P, Simon P, Löwer M et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. NATURE. 2017 Jul 13;547(7662):222-226. https://doi.org/10.1038/nature23003

Bibtex

@article{f824c5f5ac6848ca9ce08a524f84adbe,
title = "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.",
keywords = "Antibodies, Monoclonal, B7-H1 Antigen, CD8 Antigens, Cancer Vaccines, Epitopes, Humans, Immunotherapy, Melanoma, Mutation, Neoplasm Metastasis, Neoplasm Recurrence, Local, Precision Medicine, Programmed Cell Death 1 Receptor, RNA, T-Lymphocytes, Vaccination, beta 2-Microglobulin, Journal Article, Research Support, Non-U.S. Gov't",
author = "Ugur Sahin and Evelyna Derhovanessian and Matthias Miller and Bj{\"o}rn-Philipp Kloke and Petra Simon and Martin L{\"o}wer and Valesca Bukur and Tadmor, {Arbel D} and Ulrich Luxemburger and Barbara Schr{\"o}rs and Tana Omokoko and Mathias Vormehr and Christian Albrecht and Anna Paruzynski and Kuhn, {Andreas N} and Janina Buck and Sandra Heesch and Schreeb, {Katharina H} and Felicitas M{\"u}ller and Inga Ortseifer and Isabel Vogler and Eva Godehardt and Sebastian Attig and Richard Rae and Andrea Breitkreuz and Claudia Tolliver and Martin Suchan and Goran Martic and Alexander Hohberger and Patrick Sorn and Jan Diekmann and Janko Ciesla and Olga Waksmann and Alexandra-Kemmer Br{\"u}ck and Meike Witt and Martina Zillgen and Andree Rothermel and Barbara Kasemann and David Langer and Stefanie Bolte and Mustafa Diken and Sebastian Kreiter and Romina Nemecek and Christoffer Gebhardt and Stephan Grabbe and Christoph H{\"o}ller and Jochen Utikal and Christoph Huber and Carmen Loquai and {\"O}zlem T{\"u}reci",
year = "2017",
month = jul,
day = "13",
doi = "10.1038/nature23003",
language = "English",
volume = "547",
pages = "222--226",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7662",

}

RIS

TY - JOUR

T1 - Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer

AU - Sahin, Ugur

AU - Derhovanessian, Evelyna

AU - Miller, Matthias

AU - Kloke, Björn-Philipp

AU - Simon, Petra

AU - Löwer, Martin

AU - Bukur, Valesca

AU - Tadmor, Arbel D

AU - Luxemburger, Ulrich

AU - Schrörs, Barbara

AU - Omokoko, Tana

AU - Vormehr, Mathias

AU - Albrecht, Christian

AU - Paruzynski, Anna

AU - Kuhn, Andreas N

AU - Buck, Janina

AU - Heesch, Sandra

AU - Schreeb, Katharina H

AU - Müller, Felicitas

AU - Ortseifer, Inga

AU - Vogler, Isabel

AU - Godehardt, Eva

AU - Attig, Sebastian

AU - Rae, Richard

AU - Breitkreuz, Andrea

AU - Tolliver, Claudia

AU - Suchan, Martin

AU - Martic, Goran

AU - Hohberger, Alexander

AU - Sorn, Patrick

AU - Diekmann, Jan

AU - Ciesla, Janko

AU - Waksmann, Olga

AU - Brück, Alexandra-Kemmer

AU - Witt, Meike

AU - Zillgen, Martina

AU - Rothermel, Andree

AU - Kasemann, Barbara

AU - Langer, David

AU - Bolte, Stefanie

AU - Diken, Mustafa

AU - Kreiter, Sebastian

AU - Nemecek, Romina

AU - Gebhardt, Christoffer

AU - Grabbe, Stephan

AU - Höller, Christoph

AU - Utikal, Jochen

AU - Huber, Christoph

AU - Loquai, Carmen

AU - Türeci, Özlem

PY - 2017/7/13

Y1 - 2017/7/13

N2 - 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.

AB - 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.

KW - Antibodies, Monoclonal

KW - B7-H1 Antigen

KW - CD8 Antigens

KW - Cancer Vaccines

KW - Epitopes

KW - Humans

KW - Immunotherapy

KW - Melanoma

KW - Mutation

KW - Neoplasm Metastasis

KW - Neoplasm Recurrence, Local

KW - Precision Medicine

KW - Programmed Cell Death 1 Receptor

KW - RNA

KW - T-Lymphocytes

KW - Vaccination

KW - beta 2-Microglobulin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nature23003

DO - 10.1038/nature23003

M3 - SCORING: Journal article

C2 - 28678784

VL - 547

SP - 222

EP - 226

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7662

ER -