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1、自体树突状细胞疫苗治疗慢性乙型肝炎初步临床试验[作者简介]吴邦富,男,43岁,医学硕士,副主任医师,副教授,现在华中科技大学同济医学院附属东莞医院。发表论文20余篇。[摘要]目的:观察HBsAg致敏患者自体外周血单个核细胞(PBMC)来源的树突状细胞(DC)疫苗(简称抗HBV-DC)治疗慢性乙型肝炎(CHB)的临床效果。方法:11例HBeAg阳性CHB和5例HBeAg阴性CHB患者接受临床试验。取外周静脉血25ml,用密度梯度离心及贴壁法获得单核细胞,以粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4
2、(IL-4)诱导扩增出DC,第5天给予30μg的HBsAg致敏DC。第7天收获DC静脉回输,每周1次,共4次。治疗前后检测HBV标志物定量、HBV-DNA定量及肝功能。结果:好转15例,治愈1例,有效率为100%,治愈率6.25%。治疗前后HBsAg为(195.85±109.18)ng/ml和(69.98±78.65)ng/ml(t=5.14,P<0.001),1例HBsAg转阴。HBeAg阳性CHB治疗前后HBeAg为(2.56±1.66)Ncu/ml和(1.60±1.46)Ncu/ml(t=3.02,P=0
3、.013);HBeAb为(0.25±0.45)Ncu/ml和(0.82±0.74)Ncu/ml(t=2.34,P=0.041),1例HBeAb由阴转阳。HBV-DNA定量为(8.41±9.86)×107copy/ml和(3.39±5.99)×10714copy/ml(t=4.22,P=0.001)。ALT为(60.73±20.14)U/L和(74.10±49.36)U/L(t=1.26,P=0.226)。结论:抗HBV-DC静脉回输可有效地抑制CHB患者的病毒复制,降低并清除病毒抗原,促进HBeAb的产生,是一
4、种安全、有效的治疗CHB患者的方法。[关键词]树突状细胞;肝炎病毒,乙型;疫苗;慢性乙型肝炎PilotclinicalstudiesonthetherapeuticeffectofautologousdendriticcellvaccineonpatientswithchronichepatitisBWUBang-fu1,YANGJiang-ying1,ZHOUYun2,ZHANGDa-wei2,WENLing1,XIAOJiankai1,WANGQiaoyu1,ZHANGMeihua1,PANJie1,YAN
5、G-Jun21.GuangzhoumedicalcollegeaffiliatedTwelfthPeople’sHospitalofGuangzhouCity,Guangzhou510620,China;2.PubangBiologicalImmunologicTechnologyResearchCenterofGuangzhou,Guangzhou510663,China)[Abstract]Objective:ToinvestigatethetherapeuticeffectofautologousHBsA
6、g-loadeddendriticcellsvaccine(anti-HBVDCs)onpatientswithchronichepatitisB(CHB).Methods:Monocytes14wereisolatedfromperipheralbloodof11patientswithHBeAg-positiveCHBand5patientswithHBeAg-negativeCHBbyFicoll-Hypaquedensitygradientcentrifugatingandculturedwithpla
7、stic-adherencemethod.DCswereinducedandproliferatedfromthemonocyteswithgranulocyte-macrophageclonystimulatingfactor(GM-CSF)andinterleukin-4(IL-4)for7days.AfterbeingincubatedwithHBsAg,DCswereinjectedtopatients’veinfor4timesatoneweek’sinterval.HBVmarkers,HBV-DN
8、Alevels,ALTandTBILintheserumofpatientsweretestedbeforeandaftertreatment.ResultsTheeffectiveratewas100%(16/16),andthecureratewas6.25%(1/16).TheHBsAglevelswere(195.85±109.18)ng/mland(69.98±78.65)n