Application of recombinant Herpes Simplex Virus-1(HSV-1) for the treatment of malignancies outside thecentral nervous system

摘要

Attenuated HSV-1 mutants are promising novel vectors for human gene therapy of cancer. In addition to their efficacy in treatment of experimental CNS tumors, HSV mutants have shown promise in treatment of extra-CNS tumors including mesothelioma, melanoma, breast cancer, epithelial ovarian carcinoma, colon carcinoma and non small cell lung carcinoma in various animal models. HSV mutants which have been partially attenuated can function as direct oncolytic agents capable of proliferating within three-dimensional tumors and causing tumor cell death. A major advantage of these replication-restricted HSV mutants is that they can selectively replicate in tumor cells and thus, potentially express transgenes in a higher percentage of the tumor cells. Alternatively, super- attenuated HSV mutants and amplicons can function as efficient vectors for gene therapy and have the ability to host large and multiple transgenes. A multi-pronged strategy for HSV-based anti-tumor therapy is currently emerging, where multi-attenuated viruses or the oncolytic HSV mutants are used as gene therapy vectors for intratumoral delivery of immunomodulatory or chemotherapy sensitizing transgenes. HSV-based tumor therapy has been reported to induce an anti-tumor immune response in some animal models. These findings may be due to the combination of co-expression of immunomodulatory molecules, immunogenic properties of the virus, necrosis of the tumor tissue and subsequent tumor antigen presentation. Thus, HSV oncolytic agents and gene therapy vectors show great potential as anti-tumor therapies. Further studies are required to test the efficacy and safety of these agents in extra-CNS malignancies.