• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer
【24h】

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

机译：个性化RNA突变疫苗可动员针对癌症的多特异性治疗性免疫

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

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-neoepitope approach to mobilize immunity against a spectrum of cancer mutations(1,2). 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 beta 2-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.
机译：针对突变新表位的T细胞可驱动癌症免疫力。但是，突变的自发免疫识别效率低下。我们最近介绍了个性化诱变疫苗的概念，并实施了基于RNA的多新表位方法来调动针对多种癌症突变的免疫力（1,2）。在这里，我们报道了这种概念在黑色素瘤中的首次人类应用。我们建立了一个过程，其中包括对单个突变的全面鉴定，对新表位的计算预测以及为每个患者设计和生产的独特疫苗。所有患者对多种疫苗新表位的T细胞应答均高达高个位数百分比。在两名患者接种疫苗后切除的转移灶中显示了疫苗诱导的T细胞浸润和自体肿瘤细胞的新表位特异性杀伤。接种疫苗后转移事件的累积发生率大大降低，导致持续的无进展生存期。五位转移性疾病患者中有两位经历了疫苗相关的客观反应。这些患者之一由于β2-微球蛋白缺陷型黑色素瘤细胞的长出而成为晚期复发，这是获得性耐药机制。第三名患者与PD-1阻断疗法相结合，对疫苗产生了完全应答。我们的研究表明，可以利用个体突变，从而为癌症患者的个性化免疫治疗开辟道路。

著录项

  • 来源
    《Nature》 |2017年第7662期|222-226|共5页
  • 作者

    Sahin Ugur; Derhovanessian Evelyna; Miller Matthias; Kloke Bjoern-Philipp; Simon Petra; Loewer Martin; Bukur Valesca; Tadmor Arbel D.; Luxemburger Ulrich; Schroers Barbara; Omokoko Tana; Vormehr Mathias; Albrecht Christian; Paruzynski Anna; Kuhn Andreas N.; Buck Janina; Heesch Sandra; Katharina H.; Mueller 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; Burck Alexandra-Kemmer; Witt Meike; Zillgen Martina; Rothermel Andree; Kasemann Barbara; Langer David; Bolte Stefanie; Diken Mustafa; Kreiter Sebastian; Nemecek Romina; Gebhardt Christoffer; Grabbe Stephan; Holler Christoph; Utikal Jochen; Huber Christoph; Loquai Carmen; Tuereci Oezlem;

  • 作者单位

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    EUFETS GmbH, Vollmersbachstr 66, D-55743 Idar Oberstein, Germany;

    EUFETS GmbH, Vollmersbachstr 66, D-55743 Idar Oberstein, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany;

    Med Univ Vienna, Spitalgasse 23, A-1090 Vienna, Austria;

    German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany|Heidelberg Univ, Univ Med Ctr Mannheim, Theodor Kutzer Ufer 1-3, D-68135 Mannheim, Germany;

    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    Med Univ Vienna, Spitalgasse 23, A-1090 Vienna, Austria;

    German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany|Heidelberg Univ, Univ Med Ctr Mannheim, Theodor Kutzer Ufer 1-3, D-68135 Mannheim, Germany;

    Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 12, D-55131 Mainz, Germany|Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany;

    CI3 Cluster Individualized Immunointervent eV, Holderlinstr 8, D-55131 Mainz, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号