Oncolytic Viral Therapy Using Mutant Herpes Simplex Virus (HF10) for Cancer

1.在6例复发性乳腺癌患者中启动了一项使用溶瘤疱疹病毒（HF 10）的试点研究，为进一步开展研究项目做准备。在此基础上，我们积累了溶瘤病毒治疗安全性和有效性的基础研究数据和临床数据.在名古屋大学医学部的批准下，我们对三名不可切除的胰腺癌患者进行了临床试验。术中将HF 10注射到胰腺肿瘤细胞中，通过剖腹手术进行。我们评估了试验的实验室数据，包括白色血细胞计数、自然杀伤细胞、IL 12和IFN。所有患者均未观察到不良反应，并持续监测其进展情况.我们开展了新的HF-10腹腔注射基础实验.本研究利用小鼠腹膜播散性肿瘤模型，积累了生存率和毒副作用的基本数据。同时也积累了宿主对溶瘤病毒的免疫应答资料。抗病毒抗体阳性血清对病毒活性有较强的抑制作用.本研究对溶瘤病毒（HF 10）与化疗药物联合治疗肿瘤进行了体内外研究。溶瘤病毒与化疗药物联合应用较单用有更强的肿瘤杀伤作用.为了将来的药物批准，我们已经在英国完成了GMP标准纯化溶瘤病毒（HF 10）的生产过程。

1. A pilot study using oncolytic herpes virus (HF 10) was initiated, preliminary to proceeding further research projects, in six patients with recurrent breast cancer. On the basis of the result from this pilot study, we have accumulated basic research data and clinical data for oncolytic virus therapy regarding safety and effectiveness.2. We have conducted a clinical trial for three patients with non-resectable pancreatic cancer under the approval of the Nagoya University School of Medicine. The intraoperative injection of HF10 into pancreatic tumor cell was performed with laparotomy. We assessed laboratory data of the trial, including white blood cell count, natural killer cells, IL12 and IFN. We observed no adverse effects in all patients, and kept monitoring their progress.3. We have launched new fundamental experiment regarding peritoneal injection of HF 10. We have accumulated basic date of survival rate and side effect using peritoneal disseminated cancer tumor mice model. We have also accumulated the data about host immune response against oncolytic virus. Anti virus antibody positive serum strongly inhibited virus activity.4. We studied about combination therapy of oncolytic virus (HF10) and chemotherapy drug in vitro and in vivo. Combination therapy of oncolytic virus and chemotherapy drug enhanced tumor-killing effect than single use.5. For the drug approval in future, we have completed a production process of GMP standard purified oncolytic virus (HF 10) in England.