Work

Rapamycin enhances the activity of oncolytic herpes simplex virus against tumor cells that are resistant to virus replication

Year: 2010

Type: article

Abstract: Oncolytic herpes simplex virus (HSV) is currently in phase III clinical trials for development as a novel therapeutic agent against a broad range of human tumors. Although results have been promising, clinical outcome is likely to be compromised by intrinsic and acquired resistance to HSV replication, leading us to test agents that may overcome this obstacle. We found that, despite showing no effect on HSV replication in tumor cells fully permissive to the virus growth, the mTOR inhibitor rapamycin markedly increased the yield and dissemination of oncolytic HSVs in semipermissive tumor cells. Similar results were obtained in tumor-bearing mice. Co-administration of rapamycin with an HSV-derived oncolytic virus either blocked or reversed the growth of tumor xenografts established from semipermissive human tumor cells, while use of either agent alone produced only transient inhibitory effect. Together, our results suggest that rapamycin could be used to potentiate the activity of oncolytic HSVs against difficult-to-treat human tumors or perhaps to prevent the emergence of resistant tumor cells during virotherapy.

Source: International Journal of Cancer

DOI: 10.1002/ijc.25808

Authors: Xinping Fu, Lihua Tao, Armando Rivera, Xiaoliu Zhang

Institution: University of Houston

Language: English

Topic: Virus-based gene therapy research

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Cancer Institute