Enhanced efficacy of herpes simplex virus mutant HF10 combined with paclitaxel in peritoneal cancer dissemination models.
Enhanced efficacy of herpes simplex virus mutant HF10 combined with paclitaxel in peritoneal cancer dissemination models.
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发表时间：
2007-06
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通讯作者：
S. Shimoyama;F. Goshima;O. Teshigahara;H. Kasuya;Y. Kodera;A. Nakao;Y. Nishiyama
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作者：
S. Shimoyama;F. Goshima;O. Teshigahara;H. Kasuya;Y. Kodera;A. Nakao;Y. Nishiyama
背景/目的溶瘤病毒疗法在世界范围内使用。许多基因工程病毒已被评估其作为癌症新治疗剂的潜力。本课题组前期研究发现，单纯疱疹病毒（HSV）Ⅰ型克隆株HF 10具有显著的抗肿瘤作用。在这项研究中，我们研究了HF 10在体外感染和裂解小鼠结肠癌细胞CT 26的能力，并在免疫活性的结肠直肠癌动物模型中测试了其功效。此外，我们试图评估HF 10/紫杉醇联合治疗。方法体外观察HF 10对CT 26的病毒复制和细胞毒作用。在体内，携带CT 26细胞的癌性腹膜炎的BALB/c小鼠用HF 10、紫杉醇或HF 10与紫杉醇组合治疗。结果HF 10对无腹水的腹膜播散有效。与对照组、单独的HF 10和单独的紫杉醇相比，HF 10和紫杉醇的组合延长了携带CT 26癌性播散的小鼠的存活。紫杉醇不抑制HF 10的病毒复制和细胞毒性。结论：HF 10联合紫杉醇治疗晚期肿瘤疗效显著，适用于几乎所有的晚期肿瘤。这种新的联合疗法是一种潜在的划时代的癌症疗法。
BACKGROUND/AIMS Oncolytic viral therapy is used worldwide. Many genetically engineered viruses have been evaluated for their potential as a new therapeutic agent for cancer. HF10, herpes simplex virus (HSV) type-1 clone, has remarkable anti-tumor effects, based on our previous research. In this study, we investigated the ability of HF10 to infect and lyse murine colon cancer cells, CT26, in vitro, and tested its efficacy in an immuno-competent animal model of colorectal cancer. Further, we attempted to evaluate HF10/paclitaxel combination therapy. METHODOLOGY In vitro, viral replication and cytotoxicity of HF10 against CT26 was observed. In vivo, BALB/c mice harboring carcinomatous peritonitis of CT26 cells were treated with HF10, paclitaxel or HF10 combined with paclitaxel. RESULTS HF10 is effective for peritoneal dissemination without ascites. The combination of HF10 and paclitaxel prolonged survival of mice bearing carcinomatous dissemination of CT26 compared with the controls, HF10 alone and paclitaxel alone. Paclitaxel did not suppress viral replication and cytotoxicity of HF10. CONCLUSIONS These results indicate that the combination of HF10 and paclitaxel had a remarkable effect as a cancer therapy and this method is applicable to almost all advanced cancers. This new combination therapy is a potentially epoch-making cancer therapy.