聚焦超声联合程序性死亡蛋白1单克隆抗体治疗大鼠脑胶质瘤

Focused ultrasound combined with programmed cell death protein 1 monoclonal antibodies in treatment of brain glioma in rats

目的观察聚焦超声(FUS)联合程序性死亡蛋白1(PD-1)单克隆抗体药物治疗大鼠脑胶质瘤的效果。方法建立SD大鼠脑胶质瘤模型,随机分为FUS组、PD-1单抗组、联合治疗组及对照组,每组8只。于造模后第9天始对前3组分别给予干预,隔天1次,共4次:FUS组经尾静脉注入微泡后行FUS辐照,PD-1单抗组予腹腔注射PD-1单抗溶液,联合治疗组予FUS辐照后经腹腔注射PD-1单抗溶液,对照组不予干预。造模后第17天行对比动态增强MRI及病理检查,比较4组肿瘤体积及MRI血流动力学参数差异,CD4^(+)、CD8^(+)T细胞数量及Caspase-3活化细胞百分比。结果造模后第17天,联合治疗组肿瘤体积小于其余3组(P均<0.01),其相对容积转运常数rK trans高于PD-1单抗组(P=0.02)及对照组(P均<0.05),Caspase-3活化细胞百分比及肿瘤浸润淋巴细胞CD8^(+)T细胞数高于其余3组(P均<0.05)、CD4^(+)T细胞数低于其余3组(P均<0.05)。结论FUS协同抗PD-1单克隆抗体治疗有利于延缓大鼠脑胶质瘤进展。

Objective To observe the effect of focused ultrasound(FUS)combined with programmed death protein-1(PD-1)monoclonal antibody(mAb)in treatment of rat glioma models.Methods Glioma models of SD rat were established.According to intervention methods,the rats were randomly divided into FUS group,PD-1 mAb group,combined treatment group and control group.Since the 9th day after modeling,the rats were intervened once every other day for 4 times,except of those in control group.Rats in FUS group underwent FUS irradiation after injecting microbubbles into tail vein,in PD-1 mAb group underwent intraperitoneal injection of PD-1 mAb solution,while in combined treatment group underwent FUS irradiation and intraperitoneal injection of PD-1 mAb solution.On the 17th day after modeling,dynamic contrast-enhanced MRI was performed,and then pathological examination.The tumor volume and MRI hemodynamic parameters and the number of CD4^(+)and CD8^(+)T cells and percentage of Caspase-3 activated cells were observed and compared among groups.Results On the 17th day after modeling,tumor volume of combined treatment group was smaller than that of the other 3 groups(all P<0.01).The tumor relative volume transfer constant rK trans in combined treatment group was higher than that in PD-1 mAb group(P=0.02)and control group(P<0.05).The percentage of Caspase-3 activated cells and the number of CD8^(+)T cells of tumor infiltrating lymphocytes were both higher in combined treatment group than in the other 3 groups(all P<0.05),and the number of CD4^(+)T cells was lower than that in the other 3 groups(all P<0.05).Conclusion FUS combined with PD-1 mAb was helpful to delaying progression of glioma in rats.