Summary
Background
Many viruses have been engineered and evaluated for their potential as therapeutic
agents in the treatment of malignant neoplasm, including malignant melanoma.
Objective
In this study, we investigated the efficacy of HF10, an attenuated, replication-competent
HSV, in immunocompetent animal models with malignant melanoma.
Methods
For in vitro study, viral cytotoxicity assays and replication assays were performed both in human
and mouse melanoma cells. For the study in vivo, intraperitoneally disseminated or subcutaneous melanoma models were prepared in
DBA/2 mice using clone M3 cells, then HF10 was inoculated intraperitoneally or intratumorally.
Therapeutic efficacy of HF10 was assessed by survival, tumor growth, and histopathological
analysis.
Results
HF10 infection produced cytolytic effects in melanoma cells at various multiplicities
of infection (MOI). In the intraperitoneal melanoma model, all mice survived when
given intraperitoneal injections of HF10 compared with 100% fatality in the control
mice. In the subcutaneous tumor model, intratumoral inoculation of HF10 significantly
reduced tumor growth. Histology and immunohistochemistry showed tumor lysis and inflammatory
cell infiltration after intratumoral HF10 inoculation. Viral antigen was retained
at the inoculation site until 7 days post-infection. HF10-treated intraperitoneal
tumor mice were also protected against tumor rechallenge. HF10 also affected the non-inoculated
contralateral tumor when injected into the ipsilateral tumor of mice, suggesting that
HF10 can induce systemic antitumor immune responses in mice.
Conclusion
Oncolytic viral therapy using HF10 was effective in melanoma mouse models, and intratumoral
injection of HF10 induced systemic antitumor responses. These results suggest that
HF10 is a promising agent for the treatment of advanced melanoma.
Keywords
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Article info
Publication history
Published online: July 12, 2010
Accepted:
December 3,
2007
Received in revised form:
November 13,
2007
Received:
June 28,
2007
Identification
Copyright
© 2007 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
