Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice.
Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice.
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DOI：
10.1016/j.ymthe.2005.12.011
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发表时间：
2006-05
期刊：
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通讯作者：
C. Su;Lin-hui Peng;J. Sham;Xing-hua Wang;Qi Zhang;D. Chua;Chen Liu;Z. Cui;Hui-bin Xue;Hongping Wu;Qin Yang;Bai-he Zhang;Xinyuan Liu;Mengchao Wu;Q. Qian
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文献类型：
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作者：
C. Su;Lin-hui Peng;J. Sham;Xing-hua Wang;Qi Zhang;D. Chua;Chen Liu;Z. Cui;Hui-bin Xue;Hongping Wu;Qin Yang;Bai-he Zhang;Xinyuan Liu;Mengchao Wu;Q. Qian
在癌症治疗的众多基因治疗策略中，干扰素-γ(IFN-γ)的条件复制腺病毒（CRAd）基因转移可能是有用的，因为它可能产生IFN-γ介导的抗血管生成、免疫反应和CRAd介导的肿瘤溶解。在这项研究中，我们构建了一种针对端粒酶阳性癌症的人tertpromoter介导的溶瘤腺病毒，并将其与小鼠或人ifn -γ基因结合，分别产生了新的免疫基因-病毒治疗系统CNHK300-mIFN-γ和CNHK300-hIFN-γ。该系统可以特异性地靶向、复制和溶解癌细胞，同时保留正常细胞。这些系统的优点是，转基因拷贝的数量及其表达通过病毒在被感染的癌细胞内的复制而显著增加，复制的病毒后代随后可以感染肿瘤团块内的其他癌细胞。CNHK300-mIFN-γ通过选择性溶瘤、抗血管生成和免疫应答等三重机制诱导免疫缺陷和免疫正常小鼠肝癌模型中的异种移植物消退。综上所述，结合免疫基因治疗和溶瘤病毒治疗可以提高抗肿瘤疗效，这是由于CRAd溶瘤和转基因复合抗肿瘤反应之间的协同作用。
Among numerous gene therapeutic strategies for cancer treatment, gene transfer by conditionally replicative adenovirus (CRAd) ofinterferon-γ(IFN-γ) may be useful because of the possibility that it will yield IFN-γ-mediated antiangiogenesis, immune responses, and CRAd-mediated oncolysis. In this study, we constructed a humanTERTpromoter-mediated oncolytic adenovirus targeting telomerase-positive cancers and armed with a mouse or humanIFN-γgene to generate novel immune gene–viral therapeutic systems, CNHK300-mIFN-γ and CNHK300-hIFN-γ, respectively. The systems can specifically target, replicate in, and lyse cancer cells, while sparing normal cells. The advantage of these systems is that the number of transgene copies and their expression increase markedly via viral replication within infected cancer cells, and replicated viral progeny can then infect additional cancer cells within the tumor mass. CNHK300-mIFN-γ induced regression of xenografts in liver cancer models in both immunodeficient and immunocompetent mice by triplex mechanisms including selective oncolysis, antiangiogenesis, and immune responses. We conclude that combining immune gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and transgene composite antitumor responses.