抗P-gp/抗CD3双功能抗体在裸鼠体内介导人T细胞杀伤白血病耐药细胞  

Specific targeting cytotoxicity to resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody

作　　者：高瀛岱[1] 熊冬生[1] 杨铭[1] 许元富[1] 邵晓枫[1] 彭晖[1] 范冬梅[1] 杨纯正[1] 

机构地区：[1]中国医学科学院,中国协和医科大学血液学研究所实验血液学国家重点实验室,天津300020

出　　处：《中华血液学杂志》2005年第6期342-344,共3页Chinese Journal of Hematology

基　　金：国家高科技研究发展专项经费资助项目(2002AA2Z346D)

摘　　要：目的研究抗P-gp/抗CD3微型双功能抗体介导T细胞对白血病耐药细胞的特异性靶向杀伤活性。方法采用亲和层析法纯化本室构建的抗P-gp/抗CD3微型双功能抗体可溶性表达产物,并用SDSPAGE,Westernblot及活细胞间接免疫荧光法鉴定纯化产物;采用人白血病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。结果纯化的抗P-gp/抗CD3微型双功能抗体具有与Jurkat(CD3阳性)和K562/A02细胞(P-gp阳性)的结合活性,结合阳性率分别为86.25%,86.26%;在对人白血病裸鼠移植瘤模型的生物治疗中,抗P-gp/抗CD3微型双功能抗体能有效抑制耐药白血病移植瘤的生长,抑瘤率98.57%。结论抗P-gp/抗CD3微型双功能抗体在体外及动物肿瘤模型实验中能介导人T细胞有效杀伤表达P-gp抗原的耐药肿瘤细胞,具有潜在的临床应用前景。Objective To study the specific targeting cytotoxicity to drug-resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody. Methods The diabody was purified by affinity chromatography and identified by SDS-PAGE and FACS.The effect of the anti-Pgp/anti-CD3 diabody mediated lysis of Pgp-expressing tumor cells was assayed by human leukemia nude mice xenograft model in vivo. Results The diabody was produced in E.coli in a soluble functional form and could bind both Jurkat cells (CD3~ +) and K562/A02 cells(Pgp~ +). The binding rates weve 86.25% and 86.26%, respectively. It could inhibit tumor growth by 98.57% and prolonged the survival of mice bearing xenografted K562/A02 cells. Conclusion The diabody was proved to be a potent agent for mediating T lymphocyte cytotoxicity to lyse Pgp expressing tumor cells in vitro and in vivo.

关 键 词：双特异性抗体 多药抗药性 T淋巴细胞 实验性肿瘤 

分 类 号：R733.7[医药卫生—肿瘤]