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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
Nature (London), 07/2017, Letnik: 547, Številka: 7662Journal Article
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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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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