Wang Hui, Nan Fulong, Zeng Zhou, Zhang Xueming, Ke Dingxin, Zhang Shuyun, Zhou Xiaoqiong, Niu Delei, Fan Tianyu, Jiang Shasha, Zhang Xianjuan, Wang Yunyang, Wang Bin, Zhang Wanming
Department of Special Medicine, Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China.
Dazhou Integrated Traditional Chinese and Western Medicine Hospital, Dazhou, Sichuan, China.
J Med Virol. 2023 Feb;95(2):e28554. doi: 10.1002/jmv.28554.
Lung cancer is a fatal disease with the highest worldwide morbidity and mortality rates. Despite recent advances in targeted therapy and immune checkpoint inhibitors for cancer, their efficacy remained limited. Therefore, we designed a Newcastle disease virus (NDV)-modified tumor whole-cell vaccine as a therapeutic vaccine and identified its antigen presentation level to develop effective immunotherapy. Then, we calculated the therapeutic and immune-stimulating effects of NDV-modified lung cancer cell vaccine and intratumoral NDV injection combination on tumor-bearing mice. The results showed that the immunogenic cell death (ICD) expression in NDV-modified lung cancer cell vaccine stimulates dendritic cell maturation and T cell activation in vivo and in vitro. Moreover, NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could significantly inhibit tumor growth and enhance the differentiation of Th1 cells and Inflammatory cell infiltration in vivo, leading to an excellent immunotherapeutic effect. Therefore, our results revealed that NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could promote antigen presentation and induce a strong antitumor immune response, which provided a promising combined therapy strategy for tumor immunotherapy.
肺癌是一种致死性疾病,在全球范围内发病率和死亡率最高。尽管近年来癌症的靶向治疗和免疫检查点抑制剂取得了进展,但其疗效仍然有限。因此,我们设计了一种新城疫病毒(NDV)修饰的肿瘤全细胞疫苗作为治疗性疫苗,并确定其抗原呈递水平以开发有效的免疫疗法。然后,我们计算了NDV修饰的肺癌细胞疫苗与瘤内注射NDV联合使用对荷瘤小鼠的治疗和免疫刺激效果。结果表明,NDV修饰的肺癌细胞疫苗中的免疫原性细胞死亡(ICD)表达在体内和体外均可刺激树突状细胞成熟和T细胞活化。此外,NDV修饰的肺癌细胞疫苗与瘤内注射NDV联合使用可在体内显著抑制肿瘤生长,增强Th1细胞分化和炎症细胞浸润,从而产生优异的免疫治疗效果。因此,我们的结果表明,NDV修饰的肺癌细胞疫苗与瘤内注射NDV联合使用可促进抗原呈递并诱导强烈的抗肿瘤免疫反应,为肿瘤免疫治疗提供了一种有前景的联合治疗策略。