Effective treatment of disseminated peritoneal colon cancer with new replication-competent herpes simplex viruses.
OBJECTIVE
Oncolytic herpes simplex virus type 1 mutants are promising therapeutic agents for malignant tumors. Their efficacy depends on the extent of both viral replication in the tumor and induction of a host anti-tumor immune response. In this study, new replication-competent, attenuated herpes simplex virus mutants, named HF10 and Hh101, have been evaluated for their oncolytic activities.


METHODS
We determined the genome structures of the mutants and examined the survival rates of mice that were injected intraperitoneally with carcinoma and sarcoma cells and treated with the mutants. Tumors were examined by both histology and immunochemistry.


RESULTS
HF10 and Hh101 administration effectively treated disseminated peritoneal colon carcinoma in a BALB/c mouse model and all surviving mice were resistant to rechallenge of the tumor cells. The survival rate in a C3H mouse model was improved by HF10, but not Hh101.


CONCLUSIONS
HF10 and Hh101, novel agents as oncolytic viral therapy, are both safe and effective herpes simplex virus mutants for malignant tumor treatment. The Hh101, is more attenuated in its virulence than the HF10 because it is a double gene knocking-out construct. The choice of viral mutant for treatment should be made according to the type of malignancy.
Kimata
Hideto
H
Laboratory of Virology, Research Institute for Disease, Mechanism and Control, Department of Surgery II, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan.
Takakuwa
Hiroki
H
Goshima
Fumi
F
Teshigahara
Osamu
O
Nakao
Akimasa
A
Kurata
Takeshi
T
Sata
Tetsutaro
T
Nishiyama
Yukihiro
Y
D000818:Animals; D003110:Colonic Neoplasms / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012074:Remission Induction; D014407:Tumor Cells, Cultured; D014774:Virulence; D014779:Virus Replication