Nitrated T helper cell epitopes enhance the immunogenicity of HER2 vaccine and induce anti-tumor immunity
Nitrated T helper cell epitopes enhance the immunogenicity of HER2 vaccine and induce anti-tumor immunity
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硝化T辅助细胞表位增强HER2疫苗的免疫原性并诱导抗肿瘤免疫
DOI：
10.1016/j.canlet.2018.05.021
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发表时间：
2018
期刊：
影响因子：
9.7
通讯作者：
Yao Wenbing
中科院分区：
文献类型：
--
作者：
Tian Hong;He Yu;Song Xiaoda;Jiang Liangliang;Luo Jianhua;Xu Yi;Zhang Wanli;Gao Xiangdong;Yao Wenbing
人表皮生长因子受体2（HER 2）是一个有吸引力的肿瘤疫苗靶点。然而，自身免疫耐受阻止了基于HER 2蛋白的疫苗诱导持久、高效的抗肿瘤免疫。本研究证明了在通用T细胞表位（NitraTh）中引入对硝基苯丙氨酸，可以增强B细胞表位诱导的体液免疫和CTL表位诱导的细胞免疫。此外，该NitraTh表位可以在小鼠和人免疫系统中起作用。当NitraTh表位与HER 2的胞外结构域23-83融合时，有助于打破HER 2的自身耐受性，并诱导强烈的HER 2特异性体液免疫和细胞免疫。用HER 2-NitraTh疫苗接种可以显著抑制HER 2 + B16 F10肿瘤细胞的生长。这些发现对开发治疗性癌症疫苗具有重要意义。
Human epidermal growth factor receptor 2 (HER2) is an attractive target for cancer vaccine. However, autoimmune tolerance prevents vaccines based on HER2 protein from inducing long-lasting, highly effective anti-tumor immunity. In this study, we proved that the introduction ofp-nitrophenylalanine in the universal T cell epitope (named NitraTh) enhances humoral immunity induced by B cell epitope and cellular immunity induced by CTL epitope. Moreover, this NitraTh epitope can work in both mouse and human immune system. When fused with extracellular domain 23-83 of HER2, NitraTh epitope help to break the self-tolerance of HER2 and induced strong HER2 specific humoral immunity and cellular immunity. Vaccination with HER2-NitraTh can significantly inhibit the growth of HER2+B16F10 tumor cells. These findings have important implications for developing therapeutic cancer vaccines.