Research and development of an armed oncolytic virus via autophagyfor gastroenterological cancer

通过自噬治疗胃肠道癌症的武装溶瘤病毒的研发

• 批准号: 23659622
• 负责人: YAMAUE Hiroki
• 金额: $ 2.25万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23659622/
• 关键词: 癌ウイルス療法; オートファジー細胞死; ヘルペスウイルス; 癌治療用ウイルス; ウイルス療法; 癌に対するウイルス療法; 腫瘍溶解ウイルス

Refractory gastroenterological cancer such as esophageal cancer, scirrhous gastric cancer, and pancreatic cancer is characterized by rapid cancer cell infiltration. Therefore, refractory gastroenterological cancer carries a worse prognosis than other types of cancers. Viral therapy for refractory gastroenterological cancer is a promising strategy. Viral therapy using herpes simplex virus-1 (HSV -1) is especially practical for clinical application when its safety and therapeutic potency are warranted. In our experiments, we developed new type of armed oncolytic herpes simplex viruses using global genetic analysis. In addition, we confirmed that the ICP34.5 protein of HSV -1 is involved in many aspects of viral pathogenesis; promoting neurovirulence, inhibiting interferon-induced shutoff of protein synthesis, inhibiting dendritic cell maturation, and binding to Beclin 1 to interfere with autophagy . Because of its key role in neuropathogenicity, the γ34.5 gene is deleted in all oncolytic HSVs currently in clinical trial for treating malignant tumors. Unfortunately, deletion of γ34.5 attenuates virus replication in cancer cells, especially refractory gastroenterological cancer . To develop new oncolytic HSVs for use in refractory gastroenterological cancer and that replicate in refractory gastroenterological cancer , we have recently explored an armed oncolytic herpes virus expressing SOCS-3 (suppressor of cytokine signaling 3).

难治性胃肠癌如食管癌、硬质胃癌和胰腺癌的特点是癌细胞快速浸润，因此，难治性胃肠癌的预后比其他类型的癌症更差，病毒治疗是一种有前景的策略。当其安全性和治疗效力得到保证时，使用单纯疱疹病毒-1 (HSV -1) 的治疗在临床应用中特别实用。实验中，我们利用全局遗传分析开发了新型溶瘤单纯疱疹病毒。此外，我们证实HSV -1的ICP34.5蛋白参与病毒发病机制的许多方面；促进神经毒力，抑制干扰素诱导的病毒关闭。蛋白质合成、抑制树突状细胞成熟以及与 Beclin 1 结合干扰自噬 由于其在神经致病性中的关键作用，γ34.5 基因在目前所有用于治疗恶性肿瘤的溶瘤 HSV 都在临床试验中，但 γ34.5 的缺失会减弱癌细胞中的病毒复制，尤其是难治性胃肠道癌症。我们最近探索了一种表达 SOCS-3（细胞因子信号传导抑制因子 3）的武装溶瘤疱疹病毒。

项目成果

A multicenter,randomized,placebo-controlled,double-blind trial VEGFR2-epitope peptide and gemcitabine for patients with locally advanced,metastatic,or unresectable pancreatic cancer:PEGASUS-PC study.

一项针对局部晚期、转移性或不可切除胰腺癌患者的多中心、随机、安慰剂对照、双盲试验 VEGFR2 表位肽和吉西他滨：PEGASUS-PC 研究。

• 发表时间: 2012
• 作者: Shimizu A;Hirono S;Tani M;Kawai M;Okada K;Miyazawa M;Kitahata Y;Nakamura Y;Noda T;Yokoyama S;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Tani M;Hirono S;Hirono S;Okada K;Okada K;Miyazawa M;Miyazawa M;Shimizu A;山上裕機
• 通讯作者: 山上裕機

New surgical strategy for patients with pancreatic body /tail carcinoma -the impact of distalpancreatectomy with en_bloc celiac axis resection-.

胰腺体/尾癌患者的新手术策略-远端胰腺切除术与整块腹腔轴切除术的影响-。

• 发表时间: 2013
• 作者: Shimizu A;Hirono S;Tani M;Kawai M;Okada K;Miyazawa M;Kitahata Y;Nakamura Y;Noda T;Yokoyama S;Yamaue H;Yamaue H;Yamaue H;Yamaue H
• 通讯作者: Yamaue H

Phase II/IIIclinical trial with VEGFR2-epitope peptide and gemcitabine for patients with locally advanced,metastatic,or unresectable pancreatic cancer:Pegasus-PC study.

VEGFR2 表位肽和吉西他滨治疗局部晚期、转移性或不可切除胰腺癌的 II/III 期临床试验：Pegasus-PC 研究。

• 发表时间: 2013
• 作者: Shimizu A;Hirono S;Tani M;Kawai M;Okada K;Miyazawa M;Kitahata Y;Nakamura Y;Noda T;Yokoyama S;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H
• 通讯作者: Yamaue H

Borderline resectable膵がんに対する治療方針 外科治療vs化学療法

交界性可切除胰腺癌的治疗政策：手术治疗与化疗

• 发表时间: 2012
• 作者: Shimizu A;Hirono S;Tani M;Kawai M;Okada K;Miyazawa M;Kitahata Y;Nakamura Y;Noda T;Yokoyama S;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Tani M;Hirono S;Hirono S;Okada K;Okada K;Miyazawa M;Miyazawa M;Shimizu A;山上裕機;山上裕機
• 通讯作者: 山上裕機

膵・胆道癌FRONTIER4

胰腺癌和胆道癌 FRONTIER4

• 发表时间: 2013
• 作者: Shimizu A;Hirono S;Tani M;Kawai M;Okada K;Miyazawa M;Kitahata Y;Nakamura Y;Noda T;Yokoyama S;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Yamaue H;Tani M;Hirono S;Hirono S;Okada K;Okada K;Miyazawa M;Miyazawa M;Shimizu A;山上裕機;山上裕機;Mikihito Nakamori;山上裕機
• 通讯作者: 山上裕機