Xu Xiaojing, Yi Cheng, Yang Xiaoqin, Xu Jianwei, Sun Qing, Liu Yonghao, Zhao Lixiang
College of Basic Medicine and Biological Sciences, Medical Department, Soochow University, 215123 Suzhou, China.
National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Center for Tissue Engineering and Stem Cell Research, Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University, 550004 Guiyang, Guizhou, China.
Mol Ther Oncolytics. 2019 Jun 12;14:213-221. doi: 10.1016/j.omto.2019.06.001. eCollection 2019 Sep 27.
Interleukin-24 (IL-24) is a promising agent for cancer immunotherapy that induces apoptosis of tumor cells and enhances T cell activation and function. In order to improve the antitumor activity induced by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV expressing IL-24 using reverse genetics. Irradiated tumor cells infected with LX/IL-24 showed stable IL-24 expression. The cytotoxicity assay showed that LX/IL-24-infected murine melanoma cells significantly enhanced the antitumor immune response . Then, the antitumor effects of virus-infected tumor cells were examined in the murine tumor models. LX/IL-24-infected tumor cells exhibited strong antitumor effects both in prophylaxis and therapeutic models. LX/IL-24-infected tumor cells increased infiltration of CD4 T cells and CD8 T cells in tumor sites, and the antitumor activity of the tumor vaccine modified with LX/IL-24 was dependent on CD8 T cells. Taken together, our data well illustrates that LX/IL-24-modified tumor cells are a promising agent for cancer immunotherapy.
白细胞介素-24（IL-24）是一种很有前景的癌症免疫治疗药物，可诱导肿瘤细胞凋亡并增强T细胞的激活和功能。为了提高新城疫病毒（NDV）修饰的肿瘤疫苗诱导的抗肿瘤活性，我们利用反向遗传学技术构建了一种表达IL-24的重组NDV。用LX/IL-24感染的经辐照肿瘤细胞表现出稳定的IL-24表达。细胞毒性试验表明，被LX/IL-24感染的小鼠黑色素瘤细胞显著增强了抗肿瘤免疫反应。然后，在小鼠肿瘤模型中检测了病毒感染的肿瘤细胞的抗肿瘤作用。在预防和治疗模型中，被LX/IL-24感染的肿瘤细胞均表现出强大的抗肿瘤作用。被LX/IL-24感染的肿瘤细胞增加了肿瘤部位CD4 T细胞和CD8 T细胞的浸润，并且用LX/IL-24修饰的肿瘤疫苗的抗肿瘤活性依赖于CD8 T细胞。综上所述，我们的数据充分表明，经LX/IL-24修饰的肿瘤细胞是一种很有前景的癌症免疫治疗药物。
