Objectives:Despite advancements in molecular-targeted therapies and immune checkpoint inhibitors, the survival rate of patients with advanced lung cancer remains unsatisfactory. Therefore, new and effective treatment strategies are urgently needed. Both mesenchymal-epithelial transition (MET) inhibitors and oncolytic viruses exhibit immunomodulatory properties along with direct antitumor effects.Materials and Methods:The antitumor effects of a combination therapy using MDRVV, a modified vaccinia virus for oncolytic virus therapy, and tepotinib, a MET inhibitor, were evaluated in vitro and in vivo using lung cancer models.Results:The combination therapy demonstrated additive cytotoxic effects on various lung cancer cell lines in vitro and significantly suppressed tumor growth in an immunocompetent mouse model. MDRVV triggered immunogenic cell death, evidenced by the release of adenosine triphosphate (ATP) and high-mobility group box-1 (HMGB-1). Additionally, the combination therapy enhanced CD4+ and CD+ T-cell infiltration more effectively than either agent alone. MDRVV exhibited antitumor effects not only in the inoculated tumors but also in distant tumors, with the most pronounced effect observed when combined with tepotinib.Conclusions:These findings suggest that combining a MET inhibitor with oncolytic vaccinia virus represents a promising and effective strategy for improving lung cancer treatment by targeting both tumor cells and the tumor microenvironment.
目的：尽管分子靶向治疗和免疫检查点抑制剂取得了进展，但晚期肺癌患者的生存率仍不理想。因此，迫切需要新的有效治疗策略。间质-上皮转化（MET）抑制剂和溶瘤病毒均具有免疫调节特性及直接抗肿瘤作用。 材料与方法：本研究采用肺癌模型，在体外和体内评估了溶瘤病毒疗法改良型痘苗病毒MDRVV与MET抑制剂替泊替尼联合治疗的抗肿瘤效果。 结果：联合治疗在体外对多种肺癌细胞系表现出叠加的细胞毒性作用，并在免疫健全小鼠模型中显著抑制肿瘤生长。MDRVV可触发免疫原性细胞死亡，表现为三磷酸腺苷（ATP）和高迁移率族蛋白B1（HMGB-1）的释放。此外，联合治疗比单一用药更能有效增强CD4+和CD8+ T细胞浸润。MDRVV不仅在接种肿瘤中显示抗肿瘤效应，对远端肿瘤亦有效果，且与替泊替尼联用时效果最为显著。 结论：这些发现表明，MET抑制剂与溶瘤痘苗病毒联合治疗，通过同时靶向肿瘤细胞和肿瘤微环境，为改善肺癌治疗提供了一种前景广阔的有效策略。
肿瘤(癌症)患者之家