Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
Cancer Lett. 2018 Aug 28;430:79-87. doi: 10.1016/j.canlet.2018.05.021. Epub 2018 May 17.
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 of p-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.
人表皮生长因子受体 2（HER2）是癌症疫苗的一个有吸引力的靶标。然而，自身免疫耐受阻止了基于 HER2 蛋白的疫苗诱导持久、高效的抗肿瘤免疫。在这项研究中，我们证明了在通用 T 细胞表位（命名为 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，这个 NitraTh 表位可以在小鼠和人类的免疫系统中发挥作用。当与 HER2 的外显子 23-83 融合时，NitraTh 表位有助于打破 HER2 的自身耐受，诱导强烈的 HER2 特异性体液免疫和细胞免疫。用 HER2-NitraTh 进行疫苗接种可以显著抑制 HER2+B16F10 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。
