Advanced gastric cancer, especially scirrhous gastric cancer with peritoneal dissemination, remains refractory to conventional therapies. G47Δ, a third-generation oncolytic herpes simplex virus type 1, is an attractive novel therapeutic agent for solid cancer. In this study, we investigated the therapeutic potential of G47Δ for human gastric cancer. In vitro, G47Δ showed good cytopathic effects and replication capabilities in nine human gastric cancer cell lines tested. In vivo, intratumoral inoculations with G47Δ (2 × 10⁵ or 1 × 10⁶ plaque-forming units [PFU]) significantly inhibited the growth of subcutaneous tumors (MKN45, MKN74, and 44As3). To evaluate the efficacy of G47Δ for advanced-stage models of gastric cancer, we generated an orthotopic tumor model and peritoneal dissemination models of human scirrhous gastric cancer (MKN45-luc and 44As3Luc), which have features mimicking intractable scirrhous cancer patients. G47Δ (1 × 10⁶ PFU) was constantly efficacious whether administered intratumorally or intraperitoneally in the clinically relevant models. Notably, G47Δ injected intraperitoneally readily distributed to, and selectively replicated in, disseminated tumors. Furthermore, flow cytometric analyses of tumor-infiltrating cells in subcutaneous tumors revealed that intratumoral G47Δ injections markedly decreased M2 macrophages while increasing M1 macrophages and natural killer (NK) cells. These findings indicate the usefulness of G47Δ for treating human gastric cancer, including scirrhous gastric cancer and the ones in advanced stages.

晚期胃癌，特别是腹膜弥漫性硬化性胃癌，仍对传统疗法无效。G47Δ是1型的第三代溶瘤性单纯疱疹病毒，是一种有吸引力的新型固体癌症治疗剂。在这项研究中，我们研究了G47Δ对人胃癌的治疗潜力。在体外，G47Δ在测试的9种人类胃癌细胞系中显示出良好的细胞病变作用和复制能力。在体内，肿瘤内接种G47Δ（2×10 ⁵或1×10 ⁶斑块形成单位[PFU]）显着抑制皮下肿瘤（MKN45，MKN74和44As3）的生长。为了评估G47Δ在晚期胃癌模型中的疗效，我们生成了人类顽固性胃癌（MKN45-luc和44As3Luc）的原位肿瘤模型和腹膜扩散模型，它们具有模仿难治性肝硬化患者的特征。G47Δ（1×10 ⁶在临床相关模型中，无论是肿瘤内还是腹膜内给药，PFU）一直有效。值得注意的是，腹膜内注射的G47Δ容易分布到扩散的肿瘤中，并选择性地复制在扩散的肿瘤中。此外，对皮下肿瘤中的肿瘤浸润细胞的流式细胞术分析表明，瘤内G47Δ注射显着减少M2巨噬细胞，同时增加M1巨噬细胞和自然杀伤（NK）细胞。这些发现表明G47Δ在治疗人胃癌，包括硬化性胃癌和晚期胃癌中的有用性。