Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor- Specific Multi-functional CD8+ T-cell Responses
Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor- Specific Multi-functional CD8+ T-cell Responses
复制标题
将 DNA 疫苗和 AIM2 结合在 H1 纳米颗粒中，通过增强肿瘤特异性多功能 CD8( ) T 细胞反应发挥抗肾癌作用
DOI：
10.1158/1535-7163.mct-18-0832
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发表时间：
2019-02-01
影响因子：
5.7
通讯作者：
Zheng, Junnian
中科院分区：
文献类型：
--
作者：
Chai, Dafei;Shan, Hongjian;Zheng, Junnian
肾癌在高转移患者中进展迅速，且无有效的治疗策略。在这项研究中，我们设计了一种叶酸接枝PEI 600-CyD（H1）纳米粒子介导的DNA疫苗，其中含有黑色素瘤2（AIM 2）中缺失的佐剂和肿瘤特异性抗原碳酸酐酶IX（CAIX），用于肾癌治疗。分别用H1-pAIM 2/pCAIX、H1-pCAIX、H1-pAIM 2或模拟疫苗肌内免疫携带皮下人CAIX（hCAIX）-Renca肿瘤的小鼠。与对照组相比，H1-pAIM 2/pCAIX疫苗组hCAIX-Renca的肿瘤生长受到明显抑制。该疫苗激活CAIX特异性CD 8（+）T细胞增殖和CTL应答，并增强多功能CD 8（+）T细胞（表达TNF-α、IL-2和IFN-γ）的诱导。CD 8（+）T细胞耗竭导致H1-pAIM 2/pCAIX疫苗的抗肿瘤活性丧失，表明疫苗的效力依赖于CD 8（+）T细胞应答。与H1-pCAIX疫苗相比，H1-pAIM 2/pCAIX疫苗治疗还抑制了肾癌的肺转移，伴随着脾、肿瘤和支气管肺泡灌洗液中CAIX特异性多功能CD 8（+）T细胞的百分比增加。类似地，疫苗增强CAIX特异性CD 8（+）T细胞增殖和CTL应答。因此，这些结果表明H1-pAIM 2/pCAIX疫苗通过增强肿瘤特异性多功能CD 8（+）T细胞应答而显示出抗肾癌的治疗功效。这种疫苗策略可能是治疗原发性实体瘤或转移瘤的一种潜在和有前途的方法。
Renal carcinoma presents a rapid progression in patients with high metastasis with no effective therapeutic strategy. In this study, we designed a folate-grafted PEI600-CyD (H1) nanoparticle-mediated DNA vaccine containing an adjuvant of absent in melanoma 2 (AIM2) and a tumor-specific antigen of carbonic anhydrase IX (CAIX) for renal carcinoma therapy. Mice bearing subcutaneous human CAIX (hCAIX)-Renca tumor were intramuscularly immunized with H1-pAIM2/pCAIX, H1-pCAIX, H1-pAIM2, or Mock vaccine, respectively. The tumor growth of hCAIX-Renca was significantly inhibited in H1-pAIM2/pCAIX vaccine group compared with the control group. The vaccine activated CAIX-specific CD8(+) T-cell proliferation and CTL responses, and enhanced the induction of multi-functional CD8(+) T cells (expressing TNF-alpha, IL-2, and IFN-gamma). CD8(+) T-cell depletion resulted in the loss of anti-tumor activity of H1-pAIM2/pCAIX vaccine, suggesting that the efficacy of the vaccine was dependent on CD8(+) T-cell responses. Lung metastasis of renal carcinoma was also suppressed by H1-pAIM2/pCAIX vaccine treatment accompanied with the increased percentages of CAIX-specific multi-functional CD8(+) T cells in the spleen, tumor, and bronchoalveolar lavage as compared with H1-pCAIX vaccine. Similarly, the vaccine enhanced CAIX-specific CD8(+) T-cell proliferation and CTL responses. Therefore, these results indicated that H1-pAIM2/pCAIX vaccine exhibits the therapeutic efficacy of anti-renal carcinoma by enhancing tumor-specific multi-functional CD8(+) T-cell responses. This vaccine strategy could be a potential and promising approach for the therapy of primary solid or metastasis tumors.