烟台大学学报(自然科学与工程版)2024,Vol.37Issue(2):199-206,8.DOI:10.13951/j.cnki.37-1213/n.230312
表达抗PD-1抗体的溶瘤病毒在结肠癌腹腔移植瘤模型中的抗肿瘤作用
Anti-Tumor Effects of Oncolytic Viruses Engineered with Anti-PD-1 Antibody in Celiac Graft Tumor Model of Colon Cancer
摘要
Abstract
To investigate the anti-tumor effects of oncolytic viruses that express a mouse anti-PD-1 antibody(VT1093M)on a celiac graft tumor model of colon cancer,the peritoneal graft model using CT26-luc cells is es-tablished in BALB/c mice.On day 8 after inoculation,mice are randomly divided into three groups(n = 5):nor-mal saline(NS)group,VT09X virus group and VT1093M virus group.A dose of 2.5×107pfu/250 μL is admin-istered once every other day for a total of five viral injections.On day 6 after the last injection,mice are sacrificed,ascites cells and CD45+ cells from peripheral blood are extracted for in vitro killing experiments.The rechallenge experiment is performed on day 13 after the initial disappearance of fluorescence in the injected virus group.Model-ing experiments determine that the optimal seeding condition is200 μL2.5×106 cells/mL cell suspension.The re-sults indicate the potential efficacy of VT1093M oncolytic viruses in treating colon cancer.In the drug efficacy ex-periment,both the VT09X and VT1093M groups exhibit significant tumor suppression compared with the NS group.The VT1093M group shows complete tumor disappearance during the treatment period with a more pronounced tumor-suppressive effect than the VT09X group,though no significant difference is observed between the two groups.In the rechallenge experiment,no tumor regrowth is observed in the VT1093M group.In the in vitro killing experiment,the peripheral blood CD45+ cells in the injected virus group exhibit obvious killing effect on CT26-luc when the target effect ratio is 1∶40,while the killing effect on 4T1 cells is poor.These findings demonstrate that the recombinant oncolytic virus VT1093M has a significant antitumor effect in the colon cancer abdominal metastasis model and it stimulates a relatively durable specific immune response in mice.关键词
结肠癌/腹腔移植瘤/溶瘤病毒/生物发光/特异性免疫Key words
colon cancer/celiac graft tumor/oncolytic virus/bioluminescence/specific immunity分类
医药卫生引用本文复制引用
刘文琦,胡宗风,李淑珍,李劲风,李小鹏..表达抗PD-1抗体的溶瘤病毒在结肠癌腹腔移植瘤模型中的抗肿瘤作用[J].烟台大学学报(自然科学与工程版),2024,37(2):199-206,8.基金项目
山东省顶尖人才"一事一议"项目(主持人:李小鹏). (主持人:李小鹏)