Nakano K, Todo T, Chijiiwa K, Tanaka M
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Mol Ther. 2001 Apr;3(4):431-7. doi: 10.1006/mthe.2001.0303.
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.
胆囊癌一旦发生转移就极难治愈。在本文中，我们探究了溶瘤性、具有复制能力的1型单纯疱疹病毒突变体G207作为胆囊癌新治疗手段的潜力。胆囊癌细胞系（4种人类细胞系和1种仓鼠细胞系）在体外感染G207（感染复数为0.25至2.5）72小时内显示出几乎完全的细胞杀伤作用。对G207细胞病变活性的敏感性与通过lacZ表达所证明的感染效率相关。在患有已建立的皮下KIGB - 5肿瘤的免疫活性仓鼠中瘤内接种G207（1×10⁷ 空斑形成单位）可显著抑制肿瘤生长并延长生存期。重复接种（间隔4天接种3次）比单次接种显著更有效。在双侧皮下接种KIGB - 5肿瘤的仓鼠中，仅对一个肿瘤接种G207会导致未接种肿瘤以及接种肿瘤出现消退或生长减缓。然而，在无胸腺小鼠中，接种肿瘤的抗肿瘤作用大幅降低，而在远处肿瘤中则完全消失，这表明T细胞介导的免疫反应对G207的局部和全身抗肿瘤作用有很大贡献。这些结果表明，G207可能作为胆囊癌治疗的一种新策略。
