乙型肝炎表面抗原作为肿瘤免疫攻击靶点的研究  

Feasibility of using hepatitis B virus surface antigen as target antigen in immunogeng therapy against cancer

作　　者：邱双健[1] 叶胜龙[1] 汤钊猷[1] Shiguang Qian Lina Lu 

机构地区：[1]上海,复旦大学附属中山医院肝癌研究所,200032 [2]美国匹兹堡大学移植研究所

出　　处：《中华医学杂志》2002年第4期253-256,共4页National Medical Journal of China

基　　金："九七三"国家重点基础研究发展规划基金 (G19980 5 12 0 0 );"九五"国家科技攻关课题基金 (96 90 6 0 1 2 0 );国家自然科学基金 (3 9770 82 6)资助项目

摘　　要：目的　研究乙型肝炎表面抗原 (HBsAg)作为肿瘤相关抗原用于肿瘤免疫基因治疗的可能性。方法　以 1× 10 6的编码HBsAg的重组腺病毒载体转染的DC(DC HBsAg)、编码增强型绿色荧光蛋白的重组腺病毒载体转染的DC(DC EGFP)、DC以及等体积的 1×PBS静脉免疫B6小鼠 2次 ,每次间隔 1周。于最后一次免疫 1周后 ,每只小鼠皮下接种 7× 10 5B16 HBsAg或等量的B16黑色素瘤细胞。观察各免疫组小鼠皮下肿瘤的生长情况。同法以 1× 10 6的DC HBsAg和DC EGFP、1μg重组HBsAg以及等体积 1×PBS免疫B6小鼠 ,亦于最后一次免疫 1周后 ,处死部分小鼠 ,检测血清中anti HBsAg抗体滴度 ,其余小鼠皮下接种等量的B16 HBsAg ,观察肿瘤生长情况。结果　DC HBsAg疫苗可以诱导出明显强于重组HBsAg疫苗的HBsAg特异的抗瘤免疫 ,但其诱导的体液免疫水平则明显低于重组HBsAg免疫。结论　HBsAg可以作为肿瘤免疫攻击的有效靶点用于抗肿瘤免疫。Objective To investigate the feasibility of using hepatitis B virus surface antigen (HbsAg) as a tumor associated antigen in immunogene therapy against tumor. Methods (1) Dendritic cells (DCs) were extracted from bone marrow of mice and cultured. Mature DCs were transfected with adenovirus vector highly expressing HBsAg and enhanced green fluorescence protein (EGFP) (DC HBsAg). Eight C57BL/6J mice were immunized by intravenous injection of 1×10 6 DC HBsAg. Seven days after, the immunization procedure was boosted by injection of the DC HBsAg with the same dosage once more. Another eighteen mice were divided into 3 groups, 6 in each, to be injected with DC EGFP (DCs traasfected with 1×10 6 adenovecter expressing only EGFP), 1×10 6 DCs, and PBS of the same volume as controls. One week after the second injection, subcutaneous injection of 7X105 mouse melanoma cells B16 or B16 HBsAg (B16 cells expressing HBsAg) was performed to each mouse. The size of tumor was measured every 2～3 days. When the tumor grew to the size of 2cm or caused ulcer the tumor carrying mice were killed. The mice in the DC HBsAg group that showed no tumorigenesis 30 days after inoculation of B16 HBsAg were re inoculated with 7X105 B16 HBsAg. Three normal B6 mice of the same age and sex were used as controls. (2) Other patch of mice were devided into 4 groups and injected with DC HBsAg, DC EGFP, HBsAg (1 ug/mouse), and PBS in the same way as mentioned above. One week after the second injection at least 5 mice in each group were inoculated with 7X105 B16 HBsAg and 2 mice in each group were killed to have their serum anti HbsAg titers examined. Results (1) Seven days after inoculation of B16 HbsAg tumor began to grow in all mice in the three control groups. Tumor was found in 5 of the 8 mice in the DC HBsA group and the other 3 mice in this group remained free of tumor. However, the size of tumor in these 5 mice was significantly smaller than thate in other groups (P<0.01). B16 HBsAg was re inoculated to the three mic

关 键 词：抗原 肿瘤 肝炎表面抗原 乙型肝炎 基因治疗 免疫疗法 

分 类 号：R512.62[医药卫生—内科学] R735.703[医药卫生—临床医学]