抗Pgp/抗CD3微型双功能抗体在小鼠体内性质的研究  

Study on the Characteristic of Anti-Pgp/Anti-CD3 Antibody in Mouse

作　　者：秦岚[1] 赵艳津[2] 高瀛岱[2] 杨铭[2] 苏晔[2] 吕晶丽[2] 邵梦麟[1] 熊冬生[2] 杨纯正[2] 

机构地区：[1]天津市第一中心医院,300192 [2]中国医学科学院中国协和医科大学血液学研究所血液病医院实验血液学国家重点实验室

出　　处：《天津医药》2006年第9期625-627,共3页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:30400558和30400405);天津市科技攻关计划资助项目(项目编号:05YFJZJC01200和05YFGPGX06900)

摘　　要：目的:研究抗Pgp/抗CD3微型双功能抗体的体内作用。方法:125I标记抗Pgp/抗CD3微型双功能抗体采用氯胺T法,并采用昆明鼠和人K562耐药裸鼠移植瘤模型分别测定该微型双功能抗体在小鼠体内的药代动力学和体内组织分布;采用人K562耐药及敏感裸鼠移植瘤模型测定该微型双功能抗体介导的体内靶向杀伤活性及其不良反应。结果:抗Pgp/抗CD3微型双功能抗体在昆明鼠体内的半衰期为2h;尾静脉注射抗Pgp/抗CD3微型双功能抗体6h后,其在肿瘤部位的分布高于其他组织,在12h和24h时,其在肿瘤与血液分布的比率分别为2.69和8.09;抗Pgp/抗CD3微型双功能抗体能介导人T细胞有效杀伤表达Pgp抗原的K562耐药细胞。结论:抗Pgp/抗CD3微型双功能抗体能在裸鼠皮下人白血病细胞移植瘤部位富集,并能有效地抑制耐药白血病移植瘤的生长,无明显的不良反应。Objective： To study the characteristic of anti-Pgp/anti-CD3 antibody in vivo. Methods： The pharmacokinetics and distribution of the antibody were analyzed by Kunming mouse and human K562 drug resistance nude mouse xenograft model. The killing activity and ill effect of the antibody were analyzed by human K562 drug resistance and sensitive nude mouse xenograft model. Results： The anti-Pgp/anti-CD3 antibody＇s half life in Kunming mouse was 2 h. The antibody in tumor was higher than that in other tissues 6 hours after injection by caudal vein. The distribution ratios of tumor to blood at 12 h and 24 h were 2.69 and 8.09 respectively. The antibody could induce human T cell to kill K562 drug resistance humor cell which could express Pgp antigen effectively. Conclusion： The anti-Pgp/anti-CD3 antibody can concentrate in leukemia cell transplanted tumor, and also can inhibit the tumor growth without apparent toxic.

关 键 词：P糖蛋白 抗原 CD3抗体 小鼠 

分 类 号：R392-33[医药卫生—免疫学] R392[医药卫生—基础医学]