Gene Therapy with Virus Vectors for specific Disease of the Nervous System: Oncolytic Herpes Simplex Virus for Tumor Therapy

Abstract

Publisher Summary This chapter reviews the using of herpes simplex virus (HSV) as an oncolytic agent from the first preclinical work using HSV with mutations in the thymidine kinase (TK) gene, through clinical experiences with ‘‘first-generation’’ oncolytic HSV. The chapter discusses the newer (second- and third-generation) viruses with improved tumor-selective replication and/or that include the insertion of potentially therapeutic genes. Oncolytic cancer therapy has a number of potential advantages over traditional approaches to cancer treatment. Side effects are likely to be less pronounced than is often the case with chemotherapy or radiotherapy and the use of an oncolytic virus might have advantages over surgery at sites in which surgery may be impractical. This includes areas around the head and neck and spinal cord where the risks associated with the surgery can be sufficient to outweigh any potential benefit. Oncolytic agents also provide benefits over other gene-based approaches to cancer treatment in that any delivered therapeutic gene will be disseminated further through the tumor than using a nonreplicative gene delivery approach.