Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.
Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.
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发表时间：
2005
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通讯作者：
Takuji Suzuki;T. Fukuhara;Masashi Tanaka;A. Nakamura;Kenichi Akiyama;Tomohiro Sakakibara;D. Koinuma;T. Kikuchi;R. Tazawa;M. Maemondo;K. Hagiwara;Y. Saijo;T. Nukiwa
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作者：
Takuji Suzuki;T. Fukuhara;Masashi Tanaka;A. Nakamura;Kenichi Akiyama;Tomohiro Sakakibara;D. Koinuma;T. Kikuchi;R. Tazawa;M. Maemondo;K. Hagiwara;Y. Saijo;T. Nukiwa
通过抗原呈递细胞和肿瘤细胞融合进行的癌症免疫治疗已被证明可以诱导有效的抗肿瘤免疫。在这项研究中，我们表征了同基因和同种异体的小鼠巨噬细胞/树突状细胞 (DC)-癌症融合细胞的抗肿瘤作用。结果表明，在体内免疫治疗模型中，同种异体细胞作为两种类型抗原呈递细胞的融合伴侣具有优越性。在这些免疫条件下观察到肿瘤特异性 CTL 的有效诱导。此外，DC-癌融合细胞的免疫效果优于巨噬细胞-癌融合细胞。同基因和同种异体DC-癌融合细胞均比巨噬细胞-癌融合细胞诱导更高水平的IFN-γ产生。有趣的是，同种异体DC-癌融合细胞的优势在于它们能有效诱导Th1型细胞因子，但不能诱导Th2型细胞因子白细胞介素（IL）-10和IL-4，而同基因DC-癌融合细胞是Th1和Th2细胞因子的强大诱导剂。这些结果表明同种异体 DC 适合作为癌症免疫治疗中的融合细胞。为了进一步增强临床环境中的抗肿瘤免疫力，我们制备了与转移IL-12基因的癌细胞融合的DC，从而产生了分泌IL-12的DC-癌症融合细胞。使用这些基因修饰的 DC 癌融合细胞进行免疫能够在体内治疗模型中显着增强抗肿瘤效果。这种新型的产生 IL-12 的融合细胞疫苗可能是未来癌症免疫治疗的一种有前景的干预措施。
Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.