Oncolytic viral therapy for breast cancer with herpes simplex virus type 1 mutant HF 10.
OBJECTIVE
Many genetically engineered viruses have been evaluated for their potential as therapeutic agents in the treatment of malignant tumors. We applied a spontaneously generated, highly attenuated herpes simplex virus (HSV) type-1 clone, HF10, to the treatment of breast cancer. In this study, we investigated the ability of HF10 to infect and lyse human and murine breast cancer cells in vitro and tested its efficacy in an immuno-competent animal model of breast cancer.


METHODS
To assess the therapeutic efficacy of HF10 against subcutaneous tumors in vivo, mouse breast cancer cells were injected into the backs of mice, which were then treated with HF10. Tumor volume and survival rate were used as measures of the antitumor effect in the in vivo experiments. In vitro viral cytotoxity assays and replication assays were also performed in human breast cancer cell lines.


RESULTS
In the in vivo study, tumor growth was suppressed and long-term survival rates were prolonged. HF10 was effective in producing cytolytic effects in vitro at various multiplicities of infection (MOI) in all cell lines tested.


CONCLUSIONS
HF10 demonstrated antitumor effects in our animal model. The viral growth and oncolytic effect of HF10 in the human breast cancer cell line suggest that HF10 is potentially effective in the clinical treatment of human cancer. These results indicate that replication-competent HSV-1 mutants hold significant promise as cancer therapeutic agents.
Teshigahara
Osamu
O
Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan.
Goshima
Fumi
F
Takao
Kazumasa
K
Kohno
Shin-ichi
S
Kimata
Hideto
H
Nakao
Akimasa
A
Nishiyama
Yukihiro
Y
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D014709:Vero Cells; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays