溶瘤病毒治疗胰腺癌新进展

New progress in the treatment of pancreatic cancer with oncolytic virus

  • 摘要: 胰腺癌预后较差,被称为“癌中之王”。目前,其治疗手段多样,从最初闻名世界的Whipple术,到联合化疗、新辅助放化疗,再到新兴的免疫检查点抑制剂等,但各种治疗方法都有一定的局限性。近几十年来,胰腺癌的总体生存率未有明显改善。随着对肿瘤免疫的深入研究,肿瘤免疫治疗逐渐成为肿瘤治疗的焦点。而溶瘤病毒疗法作为一种新颖的免疫治疗理念,其安全性和有效性正在逐渐被学者接受。溶瘤病毒可以特异性地感染并裂解肿瘤细胞,不仅可依靠自身复制直接裂解肿瘤细胞,还能通过裂解肿瘤细胞释放免疫分子和肿瘤抗原,在不损伤正常组织的情况下进一步增强人体对肿瘤的免疫杀伤作用。此外,通过基因编辑技术可使溶瘤病毒表达丰富的外源性目的基因,进一步可加强溶瘤病毒的抗肿瘤效应。由于胰腺癌微环境的复杂性,溶瘤病毒单一疗法效果有限,联合治疗已显示出良好的临床应用前景。相对于其他肿瘤免疫疗法,溶瘤病毒疗法具有杀伤效率高、靶向性好、不良反应小、多种杀伤肿瘤途径避免耐药性和成本低廉等诸多优点,有望成为理想的肿瘤治疗新方法。笔者综合国内外相关研究和临床试验结果,对溶瘤病毒疗法的发展、相关溶瘤病毒的治疗机制及其在胰腺癌中的治疗进展进行综述。

     

    Abstract: Pancreatic cancer is called as “the king of carcinoma” owing to its poor prognosis. The current treatment methods range from the world-famous Whipple surgery to combination chemotherapy, neoadjuvant radiotherapy and chemotherapy,and emerging immunological checkpoint inhibitors. However, they all have certain limitations and the overall survival rate of pancreatic cancer has not been improved significantly in recent decades. With the further study of tumor immunology, tumor immunotherapy has gradually become the focus of cancer therapy. As a novel immunotherapy idea, oncolytic virus therapy is gradually accepted by scholars for its safety and effectiveness.Oncolytic virus can specifically infect and lyse tumor cells. It can not only directly lyse tumor cells by self-replication but also release immune molecules and tumor antigens by lysing tumor cells, which further enhance immune anti-tumor effect without damaging normal tissues. In addition, the oncolytic virus can carry the abundant exogenous target gene through gene editing technology to further enhance the anti-tumor effect of the oncolytic virus. Due to the complexity of the microenvironment of pancreatic cancer, the oncolytic virus monotherapy has limited effects, and combination therapy has shown promising prospects.Compared with other tumor immunotherapy, oncolytic virus therapy displays high killing efficiency, targeting ability and small adverse reaction, multiple anti-tumor pathways to avoid drug resistance and low cost, and is expected to become an ideal new way for oncotherapy. Based on domestic and overseas literatures, the authors have reviewed the development of ancolytic virus therapy, treatment mechanism of oncolytic virus and its advances in pancreatic cancer in this article.

     

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