Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters.
Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.
Nakano
K
K
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. kenji-n@med.kyushu-u.ac.jp
Todo
T
T
Chijiiwa
K
K
Tanaka
M
M
D000818:Animals; D002277:Carcinoma / Q000628:therapy*; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D005706:Gallbladder Neoplasms / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics*; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D013997:Time Factors; D014407:Tumor Cells, Cultured