Co-immunizing with HMGB1 enhances anti-tumor immunity of B7H3 vaccine in renal carcinoma
Co-immunizing with HMGB1 enhances anti-tumor immunity of B7H3 vaccine in renal carcinoma
复制标题
与 HMGB1 联合免疫增强 B7H3 疫苗对肾癌的抗肿瘤免疫
DOI：
10.1016/j.molimm.2021.09.002
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发表时间：
2021
影响因子：
3.6
通讯作者：
Wang Gang
中科院分区：
文献类型：
--
作者：
Sun Huanyou;Li Juan;Hu Wenwen;Yan Yinan;Guo Zengli;Zhang Zichun;Chen Yuxin;Yao Xuefan;Teng Ling;Wang Xinyuan;Li Liantao;Chai Dafei;Zheng Junnian;Wang Gang
转移性肾癌是一种恶性程度较高的肿瘤，目前尚无有效的治疗方法和策略。在本研究中，我们设计了一种叶酸接枝PEI 600-CyD（H1）纳米颗粒介导的DNA疫苗，该疫苗含有高迁移率族蛋白1（HMGB 1）佐剂和肿瘤特异性抗原B7 H3（CD 276），用于治疗肾癌。用H1-pHMGB 1/pB 7 H3、H1-pB 7 H3、H1-pHMGB 1或模拟疫苗免疫皮下携带人B7 H3（hB 7 H3）-Renca肿瘤的小鼠。与其他对照组相比，H1-pHMGB 1/pB 7 H3疫苗组的肿瘤生长受到明显抑制。H1-pHMGB 1/pB 7 H3处理组小鼠脾脏中CD 11 c +DCs的比例增加，成熟度提高。同样，HMGB 1促进B7 H3疫苗诱导肿瘤特异性CD 8 +T细胞增殖和CTL应答。此外，H1-pHMGB 1/pB 7 H3疫苗可增强功能性CD 8 +T细胞的诱导。随着CD 8 +T细胞的耗竭，H1-pHMGB 1/pB 7 H3的抗肿瘤作用也随之消失，表明CD 8 +T细胞是疫苗抗肿瘤活性的关键因素。综上所述，H1-pHMGB 1/pB 7 H3疫苗能够通过增强肿瘤特异性功能性CD 8 +T细胞应答而达到预期的抗肿瘤效果。基于纳米颗粒的H1疫苗在原发性实体瘤的治疗中可能具有巨大的潜力和前景。
Metastatic renal carcinoma is a kind of tumor with high degree of malignancy, but there are no effective treatment methods and strategies at present. In this study, we designed a folate-grafted PEI600-CyD (H1) nanoparticle-mediated DNA vaccine containing an adjuvant of high mobility group box 1 protein (HMGB1) and a tumor-specific antigen of B7H3 (CD276) for renal carcinoma therapy. Mice bearing subcutaneous human B7H3 (hB7H3)-Renca tumor were immunized with H1-pHMGB1/pB7H3, H1-pB7H3, H1-pHMGB1, or Mock vaccine. Compared to other control groups, the growth of the tumor was significantly inhibited in H1-pHMGB1/pB7H3 vaccine group. The increased proportion and mature of CD11c+DCs were observed in the spleen of H1-pHMGB1/pB7H3 treated mice. Likewise, HMGB1 promoted B7H3 vaccine to induce tumor-specific CD8+T cell proliferation and CTL responses. Beyond that, H1-pHMGB1/pB7H3 vaccine strengthened the induction of functional CD8+T cells. With the depletion of CD8+T cells, the anti-tumor effect of H1-pHMGB1/pB7H3 also disappeared, indicating that CD8+T cells are the key factor of the anti-tumor activity of the vaccine. So, to sum up, H1-pHMGB1/pB7H3 vaccine could achieve the desired anti-tumor effect by enhancing the response of tumor-specific functional CD8+T cell responses. H1 nanoparticle-based vaccines may have great potential and prospect in the treatment of primary solid tumors.