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 metastase s occur. In this paper, we explored the potential of G207, an oncolytic, re plication-competent herpes simplex virus type 1 mutant, as a new therapeuti c means for gallbladder cancer. Gallbladder carcinoma cell lines (four huma n and one hamster) showed nearly total cell killing within 72 h of G207 inf ection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cyto pathic activity correlated with the infection efficiency demonstrated by la cZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immun ocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repea ted inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutan eous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regress ion or growth reduction of uninoculated tumors as well as inoculated tumors . In athymic mice, however, the anti-tumor effect was largely reduced in in oculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemi c anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.