Gene therapy with beta-defensin 2 induces antitumor immunity and enhances local antitumor effects.
Gene therapy with beta-defensin 2 induces antitumor immunity and enhances local antitumor effects.
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DOI：
10.1089/hum.2013.161
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发表时间：
2014
影响因子：
4.2
通讯作者：
Dan-dan Li;Wei Wang;Hua-Shan Shi;Yi-jie Fu;Xiang-Hui Chen;Xiancheng Chen;Yan-tong Liu;B. Kan;Yong-Sheng Wang
中科院分区：
文献类型：
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作者：
Dan-dan Li;Wei Wang;Hua-Shan Shi;Yi-jie Fu;Xiang-Hui Chen;Xiancheng Chen;Yan-tong Liu;B. Kan;Yong-Sheng Wang
β-防御素是一种小分子抗菌肽，参与机体对肿瘤的免疫应答。在本研究中，我们使用β-防御素2（BD 2）来探索β-防御素在癌症基因治疗中的可能作用。构建了表达分泌型BD 2的重组质粒。在体外和体内测试BD 2在未成熟树突状细胞（iDC）中的生物学活性。在三种已建立的肿瘤模型中研究了其抗肿瘤作用。检测到分泌的BD 2，并在体外和体内的iDC中表现出趋化活性。肿瘤小生境中iDC的募集和活化导致显著的肿瘤生长抑制。脾细胞的连续转移和免疫细胞亚群的耗竭表明，CD 8（+）T淋巴细胞应答介导了增强的肿瘤抑制作用。此外，我们还发现肿瘤环境中iDC的趋化和成熟诱导活性有助于增强局部抗肿瘤作用。我们的研究表明，BD 2基因治疗可以介导特异性抗肿瘤免疫，增强局部抗肿瘤效应。我们的研究还表明，β-防御素可能值得进一步探索癌症免疫治疗作为有前途的免疫原。
Beta-defensins, small antimicrobial peptides, are involved in host immune responses to tumors. In this study, we used beta-defensin 2 (BD2) to explore the possible role of beta-defensins in cancer gene therapy. A recombinant plasmid expressing a secretable form of BD2 was constructed. The biological activities of BD2 in immature dendritic cells (iDCs) were tested in vitro and in vivo. The antitumor effects were investigated in three established tumor models. The secreted BD2 was detected and exhibited chemotactic activity in iDCs both in vitro and in vivo. Recruitment and activation of iDCs in tumor niches resulted in significant tumor growth inhibition. Adoptive transfer of splenocytes and depletion of immune cell subsets revealed that CD8(+) T lymphocyte responses mediated the increased tumor inhibition. Furthermore, we also found that chemotactic and maturation-inducing activities in iDCs in tumor milieu contributed to enhanced local antitumor effects. Our study indicates that gene therapy with BD2 can mediate specific antitumor immunity and augment local antitumor effects. Our study also suggested that beta-defensins may merit further exploration for cancer immunotherapy as promising immunogenes.