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An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma

Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours1,2. We are testing melanoma FixVac (BNT111)—an intravenously administered l...

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Autores principales: Sahin, Ugur (Autor) , Oehm, Petra (Autor) , Derhovanessian, Evelyna (Autor) , Jabulowsky, Robert A. (Autor) , Vormehr, Mathias (Autor) , Gold, Maike (Autor) , Maurus, Daniel (Autor) , Schwarck-Kokarakis, Doreen (Autor) , Kuhn, Andreas N. (Autor) , Omokoko, Tana (Autor) , Kranz, Lena M. (Autor) , Diken, Mustafa (Autor) , Kreiter, Sebastian (Autor) , Haas, Heinrich (Autor) , Attig, Sebastian (Autor) , Rae, Richard (Autor) , Cuk, Katarina (Autor) , Kemmer-Brück, Alexandra (Autor) , Breitkreuz, Andrea (Autor) , Tolliver, Claudia (Autor) , Caspar, Janina (Autor) , Quinkhardt, Juliane (Autor) , Hebich, Lisa (Autor) , Stein, Malte (Autor) , Hohberger, Alexander (Autor) , Vogler, Isabel (Autor) , Liebig, Inga (Autor) , Renken, Stephanie (Autor) , Sikorski, Julian (Autor) , Leierer, Melanie (Autor) , Müller, Verena (Autor) , Mitzel-Rink, Heidrun (Autor) , Miederer, Matthias (Autor) , Huber, Christoph (Autor) , Grabbe, Stephan (Autor) , Utikal, Jochen (Autor) , Pinter, Andreas (Autor) , Kaufmann, Roland (Autor) , Hassel, Jessica C. (Autor) , Loquai, Carmen (Autor) , Türeci, Özlem (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: 29 July 2020
In: Nature
Year: 2020, Volumen: 585, Número: 7823, Pages: 107-112
ISSN:1476-4687
DOI:10.1038/s41586-020-2537-9
Acceso en línea:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41586-020-2537-9
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41586-020-2537-9
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Notas de Autor:Ugur Sahin, Petra Oehm, Evelyna Derhovanessian, Robert A. Jabulowsky, Mathias Vormehr, Maike Gold, Daniel Maurus, Doreen Schwarck-Kokarakis, Andreas N. Kuhn, Tana Omokoko, Lena M. Kranz, Mustafa Diken, Sebastian Kreiter, Heinrich Haas, Sebastian Attig, Richard Rae, Katarina Cuk, Alexandra Kemmer-Brück, Andrea Breitkreuz, Claudia Tolliver, Janina Caspar, Juliane Quinkhardt, Lisa Hebich, Malte Stein, Alexander Hohberger, Isabel Vogler, Inga Liebig, Stephanie Renken, Julian Sikorski, Melanie Leierer, Verena Müller, Heidrun Mitzel-Rink, Matthias Miederer, Christoph Huber, Stephan Grabbe, Jochen Utikal, Andreas Pinter, Roland Kaufmann, Jessica C. Hassel, Carmen Loquai and Özlem Türeci
Descripción
Sumario:Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours1,2. We are testing melanoma FixVac (BNT111)—an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma—in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4+ and CD8+ T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination.
Notas:Gesehen am 02.07.2026
Descripción Física:Online Resource
ISSN:1476-4687
DOI:10.1038/s41586-020-2537-9

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