Optimization of whole-cell vaccines with CpG/αOX40/cGAMP to strengthen the anti-tumor response of CD4+ T cells in melanomas

被引:1
作者
Du, Xuedan [1 ]
Wu, Jinting [2 ]
Zhao, Ye [3 ]
Wang, Bin [2 ]
Ding, Xiaobo [2 ]
Lin, Qiuyan [4 ]
Chen, Yingyu [5 ]
Zhao, Jinduo [3 ]
Liu, Lixiao [3 ]
Mao, Xiaolu [2 ]
Fang, Zhen [2 ]
Zhang, Chunhong [6 ]
Li, Wenfeng [2 ]
机构
[1] Lishui Cent Hosp, Dept Oncol, Lishui, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Dept Oncol, Affiliated Hosp 1, 2 Fuxue Rd, Wenzhou 325000, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China
[4] Ruian City Peoples Hosp, Dept Oncol, Wenzhou, Zhejiang, Peoples R China
[5] Wenzhou Med Univ, Dept Neurosurg, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China
[6] Wenzhou Med Univ, Dept Pharm, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Whole-cell vaccines; CpG; OX40; agonist; cGAMP; Melanoma; CYTOKINE RELEASE; PD-1; BLOCKADE; TUMOR-GROWTH; CANCER; ACTIVATION; INJECTION; COMBINATION; DEATH; COSTIMULATION; ERADICATION;
D O I
10.1007/s00432-022-04117-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Methods In this study, we developed a strategy for the prevention and therapy of melanoma using a whole-cell vaccine combined with a CpG/alpha OX40/cGAMP triple adjuvant. The CpG/alpha OX40/cGAMP triple adjuvant was used to co-culture melanoma cells in vitro to induce immunogenic death of tumor cells. The mixture of inactivated tumor cells and the triple drug was an optimized tumor whole-cell vaccine, which was injected subcutaneously into mice for tumor prevention and therapy. Furthermore, we analyzed the changes of immune cells in spleen and tumor by flow cytometry and immunohistochemistry, and detected the changes of cytokines after vaccine application by cytometric bead array to explore the specific mechanism of vaccine. Results In vaccine prevention and therapy experiments, it was observed that the tumor growth was significantly inhibited in the whole-cell vaccine group, and the survival time of mice was significantly prolonged. Flow cytometry results showed that the proportion of CD4+ T cells and CD8+ T cells in tumor of mice in vaccine group was higher than that in control group, especially the CD4+ T cells. Conclusion The optimized vaccine has the unique ability to amplify tumor-specific CD4+ T cells, which improves antitumor sensitivity, and has a significant effect on the prevention and therapy of melanoma mice.
引用
收藏
页码:3337 / 3350
页数:14
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