硝基化通用T细胞表位疫苗CD47-NitraTh的设计与抑瘤活性

利用遗传密码扩充技术，将免疫原性氨基酸对硝基苯丙氨酸定点引入到通用T细胞表位，并将其与免疫检查点分子CD47分子胞外区19-140片段融合表达，构建了靶向免疫检查点CD47的疫苗CD47-NitraTh。CD47-NitraTh能够在BALB/c小鼠体内诱导产生高滴度抗体，并可显著抑制CT26结肠癌肿瘤生长，提高脾脏CD4⁺T细胞和CD8⁺T细胞的比例，同时可促进naï；ve T细胞向Th1细胞极化。值得关注的是，CD47-NitraTh不仅提高了肿瘤浸润淋巴细胞的比例，同时还降低了肿瘤组织中Treg细胞比例，意味着CD47-NitraTh疫苗能够重塑肿瘤免疫抑制性微环境。本研究结果提示，CD47-NitraTh 可以作为有效的肿瘤疫苗候选分子。

Design and antitumor effect of nitrated T helper cell epitope vaccine CD47-NitraTh

Using the genetic code extension technology, the immunogenic amino acid, p-nitrophenylalanine, was introduced into the universal T cell epitope and then fused with the fragment of the extracellular region of the immune checkpoint molecular CD47(19-140)to construct a vaccine targeting CD47. The CD47-NitraTh vaccine elicited high titer antibody in BALB/c mice, significantly inhibited CT26 colon cancer cells growth, and increased the ratio of spleen CD4⁺ T cells and CD8⁺ T cells. Meanwhile, it promoted the polarization of naï ve T cells to Th1 cells. Notably, CD47-NitraTh not only increased the proportion of tumour-infiltrating lymphocytes but also reduced the proportion of Treg cells in tumour tissues, which means that CD47-NitraTh vaccine can remodel the tumour immunosuppressive microenvironment. The results of this study suggested that CD47-NitraTh can be used as an effective tumour vaccine candidate.