Treatment of oral cancer by herpes simplex virus

单纯疱疹病毒治疗口腔癌

• 批准号: 7568856
• 负责人: EDWARD J. SHILLITOE
• 金额: $ 19.63万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7568856
• 关键词: Adverse effects; Affect; Antineoplastic Agents; Cell Cycle; Cells; Chemotherapy-Oncologic Procedure; Cytotoxic agent; Effectiveness; Environment; Epithelial Cells; Essential Genes; Goals; Herpesvirus 1; Human; Human Papillomavirus; Human Virus; Malignant Neoplasms; Methods; Mouth Neoplasms; Nerve Tissue; Nervous system structure; Oncolytic; Papillomavirus; Predisposition; Radiation; Role; Safety; Simplexvirus; Specificity; Testing; Time; Tissues; Toxic effect; Viral; Virus; cancer cell; chemotherapy; design; improved; irradiation; malignant mouth neoplasm; mutant; neoplastic cell; promoter; tumor

DESCRIPTION (provided by applicant): A new and promising approach to the treatment of oral cancer is by viruses that replicate in the tumor, thus eliminating the malignant cells. A virus that could be used for this purpose is the Herpes simplex virus type-1 (HSV-1), but it will be useful only if its potency can be increased and its safety can be improved. To increase the potency of the virus we will find how it can be combined with the use of irradiation or anti-cancer drugs in such a way as to increase its replication. The role of the cell cycle in making tumors more susceptible to the virus will be determined. To improve the safety of the virus we will find the effects of replacing the promoter of an essential gene of the virus with a fragment of the human papillomavirus, which is very specific for cancer cells. The hypothesis to be tested is that the papillomavirus promoter will allow HSV-1 to retain its toxicity for oral cancer cells while making it less toxic to cells derived from other tissues. The appropriate combination of conventional anti-cancer agents with a virus that has been modified to increase its anti-cancer specificity will produce improved opportunities for the treatment of oral cancer. This project is directed toward improved methods of treating cancer. We have modified a human virus with the goal of using it to infect cancers and eliminate them. We will find ways to make the virus more potent, but at the same time more safe.

描述（由申请人提供）：一种治疗口腔癌的新的和有前途的方法是通过在肿瘤中复制的病毒，从而消除恶性细胞。可用于此目的的病毒是单纯疱疹病毒1型（HSV-1），但只有当其效力能够增加并且其安全性能够提高时才有用。为了提高病毒的效力，我们将发现如何将其与辐射或抗癌药物的使用相结合，以增加其复制。将确定细胞周期在使肿瘤对病毒更敏感方面的作用。为了提高病毒的安全性，我们将发现用人类乳头瘤病毒的片段替换病毒的必需基因的启动子的效果，该片段对癌细胞非常特异。待测试的假设是，乳头瘤病毒启动子将允许HSV-1保留其对口腔癌细胞的毒性，同时使其对来自其他组织的细胞的毒性降低。常规抗癌剂与经修饰以增加其抗癌特异性的病毒的适当组合将产生用于治疗口腔癌的改善的机会。该项目旨在改进治疗癌症的方法。我们已经修改了一种人类病毒，目的是用它来感染癌症并消除它们。我们将找到方法使病毒更有效，但同时更安全。