Oncolytic virus therapy for biliary and pancreas cancer using a replication-competent herpes simplex virus mutant and proapoptotic reagent

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1) Antitumor efficacy of oncolytic virus therapy for gallbladder cancerGallbladder 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. Gallbaladder carcinoma cell lines (4 human and 1 hamster) showed nearly total cell killing within 72 hours of G207 infection at a MOI 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 107 pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (3 times with 4-day intervals) were significantly more effications than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one … More tumor alone with G207 caused regression or growth reduction of noninoculated tumors as well as inoculated tumors. In athymic mice, however, the antitumor 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 antitumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.2) Combination effect of oncolytic virus and proapoptotic factor for pancreas cancerA proapoptotic reagent, Tetrocarcin A, did not enhance the oncolytic effect of G207 for pancreas cancer cells in vitro. Combination of irradiation and chemotherapeutic reagents did not increase the oncolytic viral activity. These results suggest that pancreas cancer has a resistance to the proapoptotic reagent or the cytopathic effect of oncolytic virus does not depend on the apoptosis.3) Therapeutic efficacy of oncolytic virus for peritoneal disseminationWe also elucidated the therapeutic efficacy of oncolytic virus on peritoneal dissemination of gallbladder, colonic and gastric cancer, G207 prolonged the survival of animals bearing a microscopic peritoneal dissemination as compared with the controls, and some of the animals were cured. On the other hand, the animals harboring macroscopic dissemination were not cured although their survivals were also elongated than the control group.These data above have been summarized and published in Molechular Therapy 3(4), 2001 and Surgical Therapy 87 (3), 2002. Less