抗HBx单抗应用于肝癌导向治疗的实验研究

本研究应用基因工程技术制备的１７ＫＤ乙型肝炎病毒（ＨＢＶ）Ｘ蛋白（ＨＢｘＡｇ）免疫动物，成功地制备了抗－ＨＢｘ单克隆抗体，以此抗体对原发性肝癌（ＨＣＣ）组织行相应抗原检测，并同时进行乙型肝炎表面抗原（ＨＢｓＡｇ）及乙型肝炎病毒核心抗原（ＨＢｃＡｇ）的检测。在ＨＣＣ标本中，ＨＢｘＡｇ在癌内及癌周肝组织中的阳性率分别为５６％及４８％，ＨＢｓＡｇ为１６％，及７４％。ＨＢｃＡｇ仅见于癌周，阳性率仅为１８％。结果显示：ＨＢｘＡｇ在ＨＣＣ标本中的表达是ＨＢＶ标志物中最活跃的。在此基础上还进行了１３１Ｉ－ＨＢｘ单抗在荷人肝癌裸鼠体内的放射分布研究，给药后第７天瘤／血比值为１．５，瘤／肝比值为４．５，而对照组为０．４４及１．０４，表明１３１Ｉ－ＨＢｘ单抗对肝癌组织有较强的特异性亲和力，有可能成为新的载体用于肝癌的导向治疗

ASTUDY ON THE APPLICAT1ONOF 131I-HBx MONOCLONAL ANTIBODY IN IMMUNOTARGEGIAG THERAPY OF HUMAN HCC XENOGRAFTS

mouse monoclonal antibody directed against hepatitis B virus(HBV )X protein(HBxAg )was prepared. Theantibody was used to screen 50 Liver tissue sections from patients with hepatocellular carcinomaa(HCC )by im-munohisto chemistry. 28 of 50(56%)samples were HBxAg positive in tumor tissues.The positive rates of HBxAgonly in tumor tissues or in adjacent nontumor tissues were 24%and l6%. HBsAg was detected in 16% of caseswithin tumor tissues and 74%in surrounding nontumor tissues. HBcAg was only found in adjacent nontumor tis-sues,its positive rate was l8%, Those results showed that HBxAg is a common marker in liver tissue fronm pa-tients with HBV-related HCC.After anti-HBx MoAbwas radiolabeled with131I-iodine and administration ,theradioactivity of the tumor,organs and blood were counter in mini-gamma counter at day 1,3,5,7 in nude micebearing HCC xenografts,and the biodistribution and T :NT ratio was calculated. The tumor :blood ratio was 1.5and tumor :liver was l.5 on day 7 in experirmental group,respectively. Specific MoAb uptake by tumor was signif-cantly greater than nonspecific lgG(p<0.055 ) on day 7. The results were encouraging.The finding of thisstudyshow the possibility of using131I-antiHBx MoAb to target cytostatic drugs to humaan HCC.