德国BioNTech的Ugur Sahin研究组取得最新进展。他们发现RNA疫苗可促进检查点抑制剂治疗黑色素瘤的免疫力。相关论文于2020年7月29日发表于国际学术期刊《自然》杂志上。
他们正在测试一种黑色素瘤FixVac（BNT111），这是一种静脉内注射的脂质体RNA（RNA-LPX）疫苗，它针对具有四种非突变的、黑色素瘤中普遍存在的肿瘤相关抗原。这是正在进行的剂量递增晚期黑色素瘤患者的I阶段临床试验升级试验。
他们报告了来自探索性中期分析的数据，该数据表明，黑色素瘤FixVac单独或与检查点抑制剂PD1联用，可在使用检查点抑制剂（CPI）的无法切除的黑色素瘤患者中介导持久的客观反应。临床反应伴随着针对疫苗抗原的强CD4 +和CD8 + T细胞免疫诱导。在一些应答者中，抗原特异性细胞毒性T细胞应答达到过继T细胞疗法通常报道的强度，并且是持久的。
他们的发现表明，RNA-LPX疫苗接种对使用过CPI的黑色素瘤患者是一种有效的免疫疗法，并提示非突变共享肿瘤抗原通用性作为癌症疫苗接种靶标。
据了解，从概念上讲，用刺激目标免疫反应的疫苗治疗患有癌症的患者很有吸引力，但对于治疗难治性肿瘤的晚期患者，癌症疫苗试验并未取得成功。
附：英文原文
Title: An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma
Author: 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-Brck, 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 Mller, Heidrun Mitzel-Rink, Matthias Miederer, Christoph Huber, Stephan Grabbe, Jochen Utikal, Andreas Pinter, Roland Kaufmann, Jessica C. Hassel, Carmen Loquai, zlem Treci
Issue&Volume: 2020-07-29
Abstract: 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.
DOI: 10.1038/s41586-020-2537-9
Source: https://www.nature.com/articles/s41586-020-2537-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
