Campbell Family Cancer Research Institute and Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
Gene Ther. 2011 Oct;18(10):986-95. doi: 10.1038/gt.2011.53. Epub 2011 Apr 14.
Recent investigations have demonstrated that adenoviral and lentiviral vectors encoding HER-2 can be utilized in cancer immunotherapy. However, it is not known whether both viral systems elicit a similar immune response. Here, we compare the immune response in mice induced by dendritic cells (DCs) infected with either recombinant adenovirus or lentivirus encoding rat HER-2 (rHER-2). Both vaccine types yielded similar control of tumor growth, but we found clear differences in their immune responses 10 days after DC immunization. Adenovirus rHER-2-transduced DCs elicited locally and systemically high frequencies of CD4+ and CD8+ T cells, while lentivirus rHER-2-transduced DCs predominantly led to CD4+ T-cell infiltration at the tumor site. Splenocytes from mice immunized with lentivirus rHER-2-transduced DCs secreted higher levels of interferon (IFN)-γ, mainly by CD4+ T cells, following stimulation by RM-1-mHER-2 tumors. In contrast, the adenovirus vaccinated group exhibited CD4+ and CD8+ T cells that both contributed to IFN-γ production. Besides an established cellular immune response, the rHER-2/DC vaccine elicited a significant humoral response that was highest in the adenovirus group. DC subsets and regulatory T cells in the spleen were also differentially modulated in the two vaccine systems. Finally, adoptive transfer of splenocytes from both groups of immunized mice strongly inhibited in vivo tumor growth. Our results suggest that not only the target antigen but also the virus system may determine the nature and magnitude of antitumor immunity by DC vaccination.
最近的研究表明，编码 HER-2 的腺病毒和慢病毒载体可用于癌症免疫治疗。然而，尚不清楚这两种病毒系统是否会引发类似的免疫反应。在这里，我们比较了用重组腺病毒或慢病毒感染树突状细胞（DC）后在小鼠中诱导的免疫反应，这两种疫苗类型都能有效地控制肿瘤生长，但我们发现，在 DC 免疫接种 10 天后，它们的免疫反应存在明显差异。腺病毒 rHER-2 转导的 DC 可引发局部和全身高水平的 CD4+和 CD8+T 细胞，而慢病毒 rHER-2 转导的 DC 主要导致肿瘤部位的 CD4+T 细胞浸润。用慢病毒 rHER-2 转导的 DC 免疫的小鼠的脾细胞在刺激 RM-1-mHER-2 肿瘤后分泌更高水平的干扰素（IFN）-γ，主要由 CD4+T 细胞分泌。相比之下，腺病毒疫苗组显示出 CD4+和 CD8+T 细胞都有助于 IFN-γ的产生。除了已建立的细胞免疫反应外，rHER-2/DC 疫苗还引发了明显的体液反应，在腺病毒组中反应最高。两种疫苗系统也对脾中的 DC 亚群和调节性 T 细胞进行了不同的调节。最后，从两组免疫小鼠的脾细胞过继转移强烈抑制了体内肿瘤的生长。我们的研究结果表明，通过 DC 疫苗接种，不仅靶抗原，而且病毒系统也可能决定抗肿瘤免疫的性质和程度。
