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An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma
Nature ( IF 50.5 ) Pub Date : 2020-07-29 , DOI: 10.1038/s41586-020-2537-9
Ugur Sahin 1, 2, 3, 4 , Petra Oehm 1 , Evelyna Derhovanessian 1 , Robert A Jabulowsky 1 , Mathias Vormehr 1 , Maike Gold 1 , Daniel Maurus 1 , Doreen Schwarck-Kokarakis 1 , Andreas N Kuhn 1 , Tana Omokoko 1 , Lena M Kranz 1 , Mustafa Diken 1, 2 , Sebastian Kreiter 1, 2 , Heinrich Haas 1 , Sebastian Attig 2, 3 , Richard Rae 2 , Katarina Cuk 1 , Alexandra Kemmer-Brück 1 , Andrea Breitkreuz 1 , Claudia Tolliver 1 , Janina Caspar 1 , Juliane Quinkhardt 1 , Lisa Hebich 1 , Malte Stein 1 , Alexander Hohberger 2 , Isabel Vogler 1 , Inga Liebig 1 , Stephanie Renken 1 , Julian Sikorski 1 , Melanie Leierer 5 , Verena Müller 6, 7 , Heidrun Mitzel-Rink 8 , Matthias Miederer 9 , Christoph Huber 1, 2 , Stephan Grabbe 8 , Jochen Utikal 6, 7 , Andreas Pinter 10 , Roland Kaufmann 10 , Jessica C Hassel 5 , Carmen Loquai 8 , Özlem Türeci 1, 4
Affiliation  

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.

中文翻译:

RNA疫苗可驱动免疫检查点抑制剂治疗的黑色素瘤

用刺激靶向免疫反应的疫苗治疗癌症患者在概念上很有吸引力,但癌症疫苗试验在晚期难治性肿瘤患者中并未成功 1 、 2 。我们正在测试黑色素瘤 FixVac (BNT111)——一种静脉注射脂质体 RNA (RNA-LPX) 疫苗,以黑色素瘤中普遍存在的四种非突变的肿瘤相关抗原为靶点——正在进行中,首次在人体中,剂量-晚期黑色素瘤患者的升级 I 期试验(Lipo-MERIT 试验,ClinicalTrials.gov 标识符 NCT02410733)。我们在此报告了一项探索性中期分析的数据,该分析表明黑色素瘤 FixVac 单独或与检查点抑制剂 PD1 的阻断组合,介导了接受检查点抑制剂 (CPI) 治疗的不可切除黑色素瘤患者的持久客观反应。临床反应伴随着针对疫苗抗原的强 CD4 + 和 CD8 + T 细胞免疫的诱导。一些应答者的抗原特异性细胞毒性 T 细胞反应达到过继性 T 细胞治疗通常报道的程度,并且是持久的。我们的研究结果表明,RNA-LPX 疫苗接种对患有 CPI 的黑色素瘤患者是一种有效的免疫疗法,并表明非突变共享肿瘤抗原作为癌症疫苗接种靶点的普遍效用。一项 I 期试验的探索性中期分析结果表明,针对四种黑色素瘤相关抗原的 RNA 疫苗在黑色素瘤患者中产生持久的客观反应,并伴有强大的 CD4 + 和 CD8 + T 细胞免疫。
更新日期:2020-07-29
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