STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice.
STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice.
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DOI：
10.1007/s00262-015-1713-5
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Celis E
中科院分区：
文献类型：
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作者：
Wang Z;Celis E
诱导抗肿瘤CD 8 T细胞的治疗性疫苗已用于晚期黑色素瘤患者的临床试验，但临床反应率和总生存时间并没有太大改善。我们认为，这些令人沮丧的结果是由大多数疫苗产生的抗原特异性CD 8 T细胞数量不足引起的。相比之下，在急性病毒感染期间容易发生巨大的CD 8 T细胞应答。在这些感染期间产生高水平的I型干扰素（IFN-I），并且这种细胞因子不仅表现出抗病毒活性，而且还促进CD 8 T细胞应答。进行本文所述的研究以确定促进IFN-I的产生是否可以增强肽疫苗的效力。我们报告说，环二鸟苷酸单磷酸（c-di-GMP），激活干扰素基因的刺激剂，增强免疫原性和抗肿瘤作用的肽疫苗对小鼠B16黑色素瘤。c-di-GMP的协同作用需要共刺激抗CD 40抗体、佐剂poly-IC的共同给药，并且部分由IFN-I介导。这些发现表明，在模拟急性病毒感染的疫苗接种策略中，代表CD 8 T细胞表位的肽可以是大CD 8 T细胞应答的有效诱导剂。
Therapeutic vaccines to induce anti-tumor CD8 T cells have been used in clinical trials for advanced melanoma patients, but the clinical response rate and overall survival time have not improved much. We believe that these dismal outcomes are caused by inadequate number of antigen-specific CD8 T cells generated by most vaccines. In contrast, huge CD8 T cell responses readily occur during acute viral infections. High levels of type-I interferon (IFN-I) are produced during these infections, and this cytokine not only exhibits anti-viral activity but also promotes CD8 T cell responses. The studies described here were performed to determine whether promoting the production of IFN-I could enhance the potency of a peptide vaccine. We report that cyclic diguanylate monophosphate (c-di-GMP), which activates the stimulator of interferon genes, potentiated the immunogenicity and anti-tumor effects of a peptide vaccine against mouse B16 melanoma. The synergistic effects of c-di-GMP required co-administration of costimulatory anti-CD40 antibody, the adjuvant poly-IC, and were mediated in part by IFN-I. These findings demonstrate that peptides representing CD8 T cell epitopes can be effective inducers of large CD8 T cell responses in vaccination strategies that mimic acute viral infections.