Autocrine expression of both endostatin and green fluorescent protein provides a synergistic antitumor effect in a murine neuroblastoma model
Autocrine expression of both endostatin and green fluorescent protein provides a synergistic antitumor effect in a murine neuroblastoma model
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DOI：
10.1038/sj.cgt.7700346
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发表时间：
2001-07-01
影响因子：
6.4
通讯作者：
Vanin, EF
中科院分区：
文献类型：
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作者：
Davidoff, AM;Leary, MA;Vanin, EF
当联合使用时，通过不同机制起作用的方式通常可以为治疗难治性肿瘤提供协同抗肿瘤活性。在这里，我们报告了一种基因治疗方法，其中血管生成抑制剂内皮抑素、标记蛋白和强效免疫原绿色荧光蛋白（GFP）的基因在小鼠神经母细胞瘤细胞接种到同源免疫能力小鼠之前被传递到肿瘤细胞。尽管单独使用血管生成抑制或免疫调节的效果只会导致肿瘤生长的适度延迟，但当这些方法联合使用时，24只小鼠中有15只（63%）可以防止明显肿瘤的形成。内皮抑素和GFP的结合表达引起了T细胞介导的强烈免疫反应，对GFP和肿瘤细胞系特异性抗原都有反应。这为治疗小鼠提供了保护，使其免受随后未经修饰的肿瘤细胞的肿瘤攻击。这些结果表明，当在基因治疗介导的方法中使用抗血管生成和免疫治疗策略时，可以在有效的多模态抗癌方法中协同作用。
Modalities that act through different mechanisms can often provide synergistic antitumor activity for the treatment of refractory tumors when used in combination. Here we report a gene therapy approach in which the genes for the angiogenesis inhibitor, endostatin, and the marker protein and potent immunogen, green fluorescent protein (GFP), were delivered to murine neuroblastoma cells prior to inoculation of the tumor cells into syngeneic immunocompetent mice. Although the effect of either angiogenesis inhibition or immunomodulation alone resulted in only a modest delay in tumor growth, when these approaches were used in combination, prevention of the formation of appreciable tumors was effected in 15 of 24 (63%) mice. The combination of endostatin and GFP expression elicited a strong immune response that was T cell-mediated and was reactive against both GFP and tumor cell line-specific antigens. This afforded treated mice protection against subsequent tumor challenge with unmodified tumor cells. These results suggest that antiangiogenic and immunotherapy strategies, when used in a gene therapy-mediated approach, can act synergistically in an effective multimodality anticancer approach.