Xie Xin, Lv Jingwen, Zhu Wei, Tian Chao, Li Jingfeng, Liu Jiajia, Zhou Hua, Sun Chunyang, Hu Zongfeng, Li Xiaopeng
School of Pharmacy, Yantai University, Yantai Shandong 264005, China.
Beijing WellGene Company, Ltd, Beijing 100085, China.
Transl Oncol. 2022 Jan;15(1):101287. doi: 10.1016/j.tranon.2021.101287. Epub 2021 Nov 19.
Cancer immunotherapy is a new therapeutic strategy for cancer treatment that targets tumors by improving or restoring immune system function. Therapies targeting immune checkpoint molecules have exerted potent anti-tumor effects and prolonged the overall survival rate of patients. However, only a small number of patients benefit from the treatment. Oncolytic viruses exert anti-tumor effects by regulating the tumor microenvironment and affecting multiple steps of tumor immune circulation. In this study, we engineered two oncolytic viruses that express mouse anti-PD-1 antibody (VT1093M) or mouse IL-12 (VT1092M). We found that both oncolytic viruses showed significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Importantly, the intratumoral combined injection with VT1092M and VT1093M inhibited growth of the primary tumor, prevented growth of the contralateral untreated tumor, produced a vaccine-like response, activated antigen-specific T cell responses and prolonged the overall survival rate of mice. These results indicate that combination therapy with the engineered oncolytic virus may represent a potent immunotherapy strategy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.
癌症免疫疗法是一种用于癌症治疗的新策略，它通过改善或恢复免疫系统功能来靶向肿瘤。针对免疫检查点分子的疗法已发挥出强大的抗肿瘤作用，并延长了患者的总生存率。然而，只有少数患者能从该治疗中获益。溶瘤病毒通过调节肿瘤微环境和影响肿瘤免疫循环的多个步骤发挥抗肿瘤作用。在本研究中，我们构建了两种表达小鼠抗PD-1抗体（VT1093M）或小鼠IL-12（VT1092M）的溶瘤病毒。我们发现这两种溶瘤病毒在小鼠CT26结肠腺癌模型中均显示出显著的抗肿瘤作用。重要的是，瘤内联合注射VT1092M和VT1093M可抑制原发性肿瘤的生长，阻止对侧未治疗肿瘤的生长，产生类似疫苗的反应，激活抗原特异性T细胞反应并延长小鼠的总生存率。这些结果表明，工程化溶瘤病毒联合治疗可能是癌症患者，尤其是对PD-1/PD-L1阻断疗法耐药患者的一种有效的免疫治疗策略。
