Li Yuwei, Shen Yinan, Zhao Ronghua, Samudio Ismael, Jia William, Bai Xueli, Liang Tingbo
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China.
Cancer Med. 2020 May;9(9):2943-2959. doi: 10.1002/cam4.2949. Epub 2020 Mar 4.
Traditional therapies have limited efficacy in hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer, especially for advanced and refractory cancers. Through a deeper understanding of antitumor immunity and the tumor microenvironment, novel immunotherapies are becoming available for cancer treatment. Oncolytic virus (OV) therapy is an emerging type of immunotherapy that has demonstrated effective antitumor efficacy in many preclinical studies and clinical studies. Thus, it may represent a potential feasible treatment for hard to treat gastrointestinal (GI) tumors. Here, we summarize the research progress of OV therapy for the treatment of hepato-bilio-pancreatic cancers. In general, most OV therapies exhibits potent, specific oncolysis both in cell lines in vitro and the animal models in vivo. Currently, several clinical trials have suggested that OV therapy may also be effective in patients with refractory hepato-bilio-pancreatic cancer. Multiple strategies such as introducing immunostimulatory genes, modifying virus capsid and combining various other therapeutic modalities have been shown enhanced specific oncolysis and synergistic anti-cancer immune stimulation. Combining OV with other antitumor therapies may become a more effective strategy than using virus alone. Nevertheless, more studies are needed to better understand the mechanisms underlying the therapeutic effects of OV, and to design appropriate dosing and combination strategies.
传统疗法在肝细胞癌、胰腺癌和胆管癌中的疗效有限，尤其是对于晚期和难治性癌症。通过对抗肿瘤免疫和肿瘤微环境的深入了解，新型免疫疗法正逐渐应用于癌症治疗。溶瘤病毒（OV）疗法是一种新兴的免疫疗法，已在许多临床前研究和临床研究中显示出有效的抗肿瘤疗效。因此，它可能是治疗难治性胃肠道（GI）肿瘤的一种潜在可行的治疗方法。在此，我们总结了OV疗法治疗肝胰胆管癌的研究进展。一般来说，大多数OV疗法在体外细胞系和体内动物模型中都表现出强大的、特异性的溶瘤作用。目前，多项临床试验表明，OV疗法对难治性肝胰胆管癌患者也可能有效。引入免疫刺激基因、修饰病毒衣壳以及联合其他多种治疗方式等多种策略已显示出增强的特异性溶瘤作用和协同抗癌免疫刺激作用。将OV与其他抗肿瘤疗法联合使用可能比单独使用病毒成为更有效的策略。然而，需要更多的研究来更好地理解OV治疗效果的潜在机制，并设计合适的给药和联合策略。
