Journal
CANCER GENE THERAPY
Volume 18, Issue 2, Pages 77-86Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2010.53
Keywords
oncolytic virotherapy; ovarian cancer; cell carriers; herpes simplex virus
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Funding
- Ministry of Education, Science and Culture of Japan [21592128]
- Grants-in-Aid for Scientific Research [21592128] Funding Source: KAKEN
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Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. We have developed replication-competent attenuated herpes simplex virus type 1 (HSV-1) mutants, named HF10 and Hh101, which have been evaluated for their oncolytic activities. However, the host immune system remains a significant obstacle to effective intraperitoneal administration of these viruses in the clinical setting. In this study, we investigated the use of these HSV-1 mutants as oncolytic agents against ovarian cancer and the use of human peritoneal mesothelial cells (MCs) as carrier cells for intraperitoneal therapy. MCs were efficiently infected with HSV-1 mutants, and MCs loaded with HSV-1 mutants caused cell killing adequately when cocultured with cancer cells in the presence or absence of HSV antibodies. In a mouse xenograft model of ovarian cancer, the injection of infected carrier cells led to a significant reduction of tumor volume and prolonged survival in comparison with the injection of virus alone. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on ovarian cancer, which may be further enhanced by the utilization of a carrier cell delivery system, based on amplification of viral load and possibly on avoidance of neutralizing antibodies. Cancer Gene Therapy (2011) 18, 77-86; doi: 10.1038/cgt.2010.53; published online 1 October 2010
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