Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
J Control Release. 2023 Jul;359:359-372. doi: 10.1016/j.jconrel.2023.05.044. Epub 2023 Jun 14.
Whole tumor cells can act as effective antigen depots and have been regarded as prospective candidate for cancer vaccines. However, the clinical outcomes of whole tumor cell vaccine were restricted by the poor immunogenicity and potential in vivo oncogenicity risks. Herein, a simple and effective cancer vaccine named frozen dying tumor cells (FDT) was constructed to initiate a cascade of immune attacks against cancer. By introducing immunogenic dying tumor cells and integrating cryogenic freezing technology, FDT was endowed with high immunogenicity, good in vivo safety, and long-time storage superiority. In syngeneic mice with malignant melanoma, FDT primed the polarization of follicular helper T cells and the differentiation of germinal center B cells in lymph nodes, and promoted the infiltration of cytotoxic CD8 T cells in the tumor microenvironment, triggering the dual activation of humoral and cellular immunity. Of note, when combined with cytokines and immune checkpoint inhibitors, the FDT vaccine achieved 100% eradication of pre-existing tumors in mice, as demonstrated in the peritoneal metastasis model of colorectal carcinoma. Taken together, our work suggests an efficient cancer vaccine inspired by dying tumor cells and provides an alternative treatment candidate for cancer.
整个肿瘤细胞可以作为有效的抗原储存库，被认为是癌症疫苗的潜在候选物。然而，由于肿瘤细胞的免疫原性差和潜在的体内致瘤性风险，整体肿瘤细胞疫苗的临床效果受到限制。在此，构建了一种名为冷冻死亡肿瘤细胞（FDT）的简单有效的癌症疫苗，以引发针对癌症的免疫攻击级联反应。通过引入免疫原性死亡肿瘤细胞并整合低温冷冻技术，FDT 具有高免疫原性、良好的体内安全性和长时间储存优势。在具有恶性黑色素瘤的同基因小鼠中，FDT 诱导了滤泡辅助 T 细胞的极化和淋巴结生发中心 B 细胞的分化，并促进了细胞毒性 CD8 T 细胞在肿瘤微环境中的浸润，引发了体液和细胞免疫的双重激活。值得注意的是，当与细胞因子和免疫检查点抑制剂联合使用时，FDT 疫苗在结直肠癌腹膜转移模型中实现了对小鼠预先存在肿瘤的 100%消除。综上所述，我们的工作提出了一种受死亡肿瘤细胞启发的高效癌症疫苗，并为癌症提供了一种替代治疗候选物。
