表达PD1抗体的重组流感病毒株靶向胃癌溶瘤效果的研究

Oncolytic effect of recombinant influenza virus carrying PD1 antibody on gastric cancer

目的探究表达PD1抗体的重组流感病毒株在体内外靶向杀伤胃癌细胞的效果。方法使用MTS方法检测重组流感病毒rFlu-aPD1杀伤胃癌细胞的效果;流式细胞术检测重组流感病毒rFlu-aPD1诱导胃癌细胞凋亡的效果。利用小鼠胃癌模型,评价重组流感病毒在体内对胃癌的抑制效果。结果MTS结果表明,rFlu-aPD1可选择性杀伤胃癌细胞,而对正常胃细胞无明显影响;凋亡实验显示,rFlu-aPD1主要通过激活细胞凋亡途径诱导胃癌细胞死亡。动物实验显示,重组流感病毒rFluaPD1可明显降低胃癌小鼠的肿瘤体积和质量,且肿瘤部位的病毒载量明显高于其他组织。结论表达PD1抗体的重组流感病毒株rFlu-aPD1,在体内外均可杀伤胃癌细胞,有望为溶瘤病毒靶向治疗胃癌和肿瘤免疫治疗提供新方法。

Gastric cancer is one of the malignant tumors with the highest incidence in the world,ranking fifth in incidence and fourth in mortality.Although the comprehensive treatment of gastric cancer has achieved certain results,there is an urgent need for new strategies to prolong the survival time and improve the prognosis.The purpose of this article is to investigate the effect of a recombinant influenza virus strain expressing PD1 antibody(rFlu-aPD1)on gastric cancer in vivo and in vitro.MTS method was used to detect the killing effect of the recombinant influenza virus on gastric cancer cells;flow cytometry was used to detect the effect of the recombinant influenza virus on the apoptosis of gastric cancer cells.Mouse gastric cancer model was employed to evaluate the inhibitory effect of recombinant influenza virus on gastric cancer in vivo.Data showed that rFlu-aPD1 could selectively kill gastric cancer cells,but had no obvious effect on normal gastric cells.Apoptosis experiments showed that rFlu-aPD1 induces the death of gastric cancer cells mainly by activating the apoptotic pathway.While animal experiments showed that the recombinant influenza virus rFlu-aPD1 could significantly reduce the tumor volume and mass in mice with gastric cancer,and the viral load at the tumor site was significantly higher than other tissues.Taken together,the recombinant influenza virus strain rFlu-aPD1 expressing PD1 antibody can kill gastric cancer cells in vivo and in vitro,which is expected to provide a new method for oncolytic virus targeted therapy of gastric cancer and tumor immunotherapy.