Song Shuxia, Wang Yue, Zhang Yan, Wang Fang, He Ying, Ren Ding, Guo Yingjun, Sun Shuhan
Department of Medical Genetics, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
Cancer Lett. 2007 Oct 18;256(1):90-100. doi: 10.1016/j.canlet.2007.06.004. Epub 2007 Jul 25.
The present study aims at establishing a novel vaccine procedure based on HBc-VLP-pulsed DCs. Immature mice BMDCs could capture HBc-VLP or HBc-VLP packaging CpG efficiently and present the antigen to syngeneic mice spleen T cells in vitro. Immunization with DCs showed that compared to VLP-pulsed DCs, VLP packaging CpG-pulsed DCs elicit stronger T-cell responses in vivo, as measured by both intracellular production of IFN-gamma and in vivo killing assays by Ag-specific T cells. In the B16-pIR-HH tumor therapy model, the growth of established tumors was significantly inhibited by single immunization of DCs pulsed with HBc-VLP packaged with CpG, resulting in significantly longer survival of immunized animals and strikingly, high frequencies (>10% of CD8(+) cells) of protective CTL could be induced and maintained. The mice immunized with DCs treated with HBc-VLP, however, trigger an antitumor effect at the early phase of vaccination, after 20 days of tumor injection, the tumor growth inhibition of VLP-pulsed DCs vaccination was decreased gradually and the fact could be interpreted by the decreasing number of antigen-specific CD8(+) T-cell and IFN-gamma(+)-producing CD8(+) T cell. This study therefore shows that the use of HBc-VLP packaging CpG-pulsed DCs could facilitate the development of effective T-cell-based vaccines.
本研究旨在建立一种基于乙肝核心病毒样颗粒（HBc-VLP）脉冲树突状细胞（DCs）的新型疫苗程序。未成熟小鼠骨髓来源的树突状细胞（BMDCs）能够有效捕获HBc-VLP或HBc-VLP包裹的CpG，并在体外将抗原呈递给同基因小鼠脾脏T细胞。用树突状细胞进行免疫接种表明，与VLP脉冲的树突状细胞相比，VLP包裹CpG脉冲的树突状细胞在体内引发更强的T细胞反应，这通过细胞内干扰素-γ的产生以及抗原特异性T细胞的体内杀伤试验来衡量。在B16-pIR-HH肿瘤治疗模型中，用包裹有CpG的HBc-VLP脉冲的树突状细胞单次免疫可显著抑制已建立肿瘤的生长，导致免疫动物的存活时间显著延长，而且令人惊讶的是，可诱导并维持高频率（>10%的CD8(+)细胞）的保护性细胞毒性T淋巴细胞（CTL）。然而，用HBc-VLP处理的树突状细胞免疫的小鼠在接种疫苗的早期触发抗肿瘤作用，在肿瘤注射20天后，VLP脉冲树突状细胞疫苗接种对肿瘤生长的抑制作用逐渐降低，这一事实可以通过抗原特异性CD8(+) T细胞和产生干扰素-γ(+)的CD8(+) T细胞数量的减少来解释。因此，本研究表明，使用HBc-VLP包裹CpG脉冲的树突状细胞可促进基于有效T细胞的疫苗的开发。
