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 tumours 1 , 2 . We are testing melanoma FixVac (BNT111)—an intravenously administer...

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Published in:	Nature (London) Vol. 585; no. 7823; pp. 107 - 112
Main Authors:	Sahin, Ugur, Oehm, Petra, Derhovanessian, Evelyna, Jabulowsky, Robert A., Vormehr, Mathias, Gold, Maike, Maurus, Daniel, Schwarck-Kokarakis, Doreen, Kuhn, Andreas N., Omokoko, Tana, Kranz, Lena M., Diken, Mustafa, Kreiter, Sebastian, Haas, Heinrich, Attig, Sebastian, Rae, Richard, Cuk, Katarina, Kemmer-Brück, Alexandra, Breitkreuz, Andrea, Tolliver, Claudia, Caspar, Janina, Quinkhardt, Juliane, Hebich, Lisa, Stein, Malte, Hohberger, Alexander, Vogler, Isabel, Liebig, Inga, Renken, Stephanie, Sikorski, Julian, Leierer, Melanie, Müller, Verena, Mitzel-Rink, Heidrun, Miederer, Matthias, Huber, Christoph, Grabbe, Stephan, Utikal, Jochen, Pinter, Andreas, Kaufmann, Roland, Hassel, Jessica C., Loquai, Carmen, Türeci, Özlem
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 03.09.2020 Nature Publishing Group
Subjects:	13/21 13/31 38/23 59/57 59/78 631/154/51/2293 631/250/251/1567 631/67/1059/2325 Antibodies Antigens Antigens, Neoplasm - immunology Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Cancer Cancer vaccines Cancer Vaccines - administration & dosage Cancer Vaccines - adverse effects Cancer Vaccines - genetics Cancer Vaccines - immunology CD4 antigen CD8 antigen Cell therapy Clinical trials Combined Modality Therapy Cytokines Cytotoxicity Dendritic cells Humanities and Social Sciences Humans Immune checkpoint Immune response Immune system Immunity Immunotherapy Inhibitors Lymphocytes Lymphocytes T Melanoma Melanoma - drug therapy Melanoma - immunology Melanoma - pathology Melanoma - therapy Metabolism Metastasis mRNA vaccines multidisciplinary Neoplasm Staging Patients PD-1 protein Programmed Cell Death 1 Receptor - antagonists & inhibitors Proteins Ribonucleic acid RNA RNA, Neoplasm - genetics Science Science (multidisciplinary) T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes, Cytotoxic - cytology T-Lymphocytes, Cytotoxic - immunology Tumor necrosis factor-TNF Tumors Vaccination Vaccines
ISSN:	0028-0836, 1476-4687, 1476-4687
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Summary:	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 tumours 1 , 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. Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4 + and CD8 + T-cell immunity.
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ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-020-2537-9