新型重组溶瘤痘苗病毒感染联合免疫效应细胞及免疫检查点阻断三联治疗胃癌的研究  

Experimental Study on Treatment of Gastric Cancer with New Recombinant Oncolytic Vaccinia Virus Infection Combined with Immune Effective Cells and Immune Checkpoint Blocking

作　　者：张林 侯艳红 吴凯 张静 ZHANG Lin;HOU Yanhong;WU Kai;ZHANG Jing(The Eighth Medical Center,PLA General Hospital,Beijing 100091,China)

机构地区：[1]中国人民解放军总医院第八医学中心,北京100091

出　　处：《肿瘤防治研究》2024年第6期426-431,共6页Cancer Research on Prevention and Treatment

基　　金：首都卫生发展科研专项基金(2011-5007-01)。

摘　　要：目的探讨溶瘤病毒感染、免疫效应细胞补充及免疫检查点阻断三者联合策略在胃癌治疗中的意义。方法以既往实验获得的痘苗病毒为基础构建的携带T淋巴细胞趋化因子CXCL9基因和白细胞介素7(IL-7)基因的重组溶瘤痘苗病毒(VV-IL7-CXCL9)干预治疗裸鼠皮下种植瘤方式建立的胃癌荷瘤动物模型。实验建立重组溶瘤痘苗病毒瘤内注射+细胞毒性T淋巴细胞(CTL)+免疫检查点阻断剂(PD-1单抗)三联干预组、三种措施单独干预组、二联干预组及空白对照组。按照既定分组给药干预后采用肿瘤生长曲线法、肿瘤抑制率法及动物活体发光法检测肿瘤治疗效果并采取ELISA法检测各组动物血清及组织匀浆CXCL9和IL-7两分子浓度。结果动物模型治疗干预结果显示重组溶瘤痘病毒+细胞毒性T淋巴细胞(CTL)+免疫检查点阻断剂(PD-1单抗)三联干预组肿瘤生长明显减缓,显著慢于其他干预组及空白对照组。结论在胃癌动物模型干预实验中采用重组溶瘤痘病毒瘤内注射+细胞毒性T淋巴细胞(CTL)+免疫检查点阻断剂(PD-1单抗)三联干预的生物免疫治疗策略具有强烈的抑瘤作用。Objective To explore the significance of the combined strategy of oncolytic virus infection,immune effector cell supplement,and immune checkpoint blocking in the treatment of gastric cancer.Methods A tumor-bearing nude mouse model of gastric cancer was treated with recombinant oncolytic vaccinia virus carrying the CXCL9 gene of T lymphocyte chemokine and IL-7gene(VV-IL7-CXCL9)obtained in previous experiments.We established a triple-intervention group of recombinant oncolytic vaccinia virus intratumoral injection+cytotoxic T lymphocyte(CTL)+immune checkpoint blocker(PD-1 monoclonal antibody),a single-intervention group of three measures,a dual-intervention group,and a blank control group.After the intervention,tumor-growth curve method,tumor-inhibition rate method,and bioluminescence method were used to detect the tumor treatment effect.ELISA was used to detect CXCL9 and IL-7 molecule concentration in the serum and tissue homogenate of animals in each group.Results The therapeutic results of animal models showed that the tumor growth in the triple-intervention group of recombinant oncolytic poxvirus+CTL+immune checkpoint blocker(PD-1 monoclonal antibody)was significantly slower than those in the other intervention and the blank control group.Conclusion The combination of recombinant oncolytic poxvirus intratumoral injection+CTL+immune checkpoint blocker(PD-1 monoclonal antibody)exert a strong antitumor effect in intervention experiments on gastric-cancer animal models.

关 键 词：胃癌 溶瘤痘病毒 免疫效应细胞 免疫检查点阻断治疗 

分 类 号：R735.2[医药卫生—肿瘤]