School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518000, China.
School of Pharmaceutical Sciences, International Cancer Center, Health Science Center, Shenzhen University, Shenzhen 518000, China.
Cells. 2022 Jun 21;11(13):1986. doi: 10.3390/cells11131986.
A single-protein or -peptide vaccine is not sufficient to arouse immune responses in cancer therapy. A whole-tumor-cell vaccine with complete cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this study, we used 5-azacitidine to stimulate B16-F10 melanoma cells to express toll-like receptor (TLR) 3 on the cell surface and then chemically linked SZU-106, a small-molecule TLR7 agonist, to the cell surface with a pegylated linker to produce a novel whole-tumor-cell vaccine, abbreviated as Aza-BFcell-106. The vaccine stimulated mouse splenic lymphocytes and bone marrow-derived dendritic cells to secrete cytokines, promoted the maturation of dendritic cells and enhanced the capability of dendritic cells to present antigens. In a mouse model of melanoma, the vaccine effectively inhibited tumor growth, decreased tumor volume and prolonged survival. Further combination of the vaccine with a chemokine inhibitor, reparixin, significantly increased the infiltration of CD4+ and CD8+ T cells into the tumor environment, while the antitumor effect was significantly enhanced. The whole-tumor-cell vaccine Aza-BFcell-106 induced immune-activating responses in both in vitro and in vivo experiments, indicating that this vaccine has great potential to treat advanced malignant tumors.
单一蛋白质或肽疫苗不足以在癌症治疗中引起免疫反应。全肿瘤细胞疫苗具有完整的肿瘤细胞抗原和所有构象，可引发强大的免疫反应，是治疗晚期恶性肿瘤的有前途的方法。在这项研究中，我们使用 5-氮杂胞苷刺激 B16-F10 黑色素瘤细胞在细胞表面表达 Toll 样受体 (TLR) 3，然后用聚乙二醇化接头将小分子 TLR7 激动剂 SZU-106 化学连接到细胞表面，产生一种新型的全肿瘤细胞疫苗，简称 Aza-BFcell-106。该疫苗刺激小鼠脾淋巴细胞和骨髓来源的树突状细胞分泌细胞因子，促进树突状细胞成熟，并增强树突状细胞呈现抗原的能力。在黑色素瘤小鼠模型中，该疫苗有效抑制肿瘤生长，减小肿瘤体积并延长生存时间。进一步将疫苗与趋化因子抑制剂雷帕霉素联合使用，可显著增加 CD4+和 CD8+T 细胞浸润肿瘤环境，同时显著增强抗肿瘤作用。全肿瘤细胞疫苗 Aza-BFcell-106 在体内外实验中均诱导免疫激活反应，表明该疫苗具有治疗晚期恶性肿瘤的巨大潜力。
