新型抗淋巴瘤药物anti-CD19(Fab)-LDM的靶向分布研究  

Targeting distribution of anti-CD19(Fab)-LDM: a new anti-lymphoma drug

作　　者：时玉峥 刘红芹 姜琳琳[1] 杨铭[1] 范冬梅[1] 屈浩 石琳 石钏 冯春玲 刘芸 熊冬生[1] 廖晓龙[1,2] 

机构地区：[1]中国医学科学院北京协和医学院血液病医院血液学研究所,天津300020 [2]协和干细胞基因工程有限公司,天津300384

出　　处：《中国药理学通报》2014年第7期917-921,共5页Chinese Pharmacological Bulletin

基　　金：国家科技部"十二五""重大新药创制"项目科技重大专项资助(No 2011ZX09506-003)

摘　　要：目的研究抗体毒素偶联新型药物anti-CD19(Fab)-LDM体内外靶向CD19+B淋巴瘤细胞的能力。方法制备Cy5标记的anti-CD19(Fab)-LDP(LDP为LDM辅基蛋白),体外流式细胞仪分析其与人淋巴瘤Raji细胞表面CD19抗原的结合能力;体内建立裸鼠淋巴瘤皮下移植瘤模型,应用活体动物成像系统观察Cy5标记的anti-CD19(Fab)-LDP在荷瘤小鼠体内的靶向分布。结果 Cy5标记的anti-CD19(Fab)-LDP能有效与淋巴瘤Raji细胞膜表面的CD19抗原结合;成功建立人淋巴瘤Raji细胞皮下移植瘤模型,体内活体成像结果表明,融合蛋白anti-CD19(Fab)-LDP可靶向定位到肿瘤部位。结论体内外实验证实anti-CD19(Fab)-LDP能很好的靶向CD19+的淋巴瘤细胞,此抗体毒素偶联药物anti-CD19(Fab)-LDM有希望成为治疗恶性淋巴瘤的新型药物。Aim To study targeting capability of anti-CD19 （Fab）-LDMto CD19 ＋B lymphoma cells in vi-vo and in vitro.Methods Flow cytometry was em-ployed to determine the affinity of Cy5 labeled anti-CD19 （Fab）-LDP to human lymphoma Raji cells.And the optical imaging system was used to analyze the dis-tribution of Cy5-anti-CD19 （Fab ）-LDP in lymphoma-transplanted xenograft nude mice in vivo.Results The results of flow cytometry demonstrated that Cy5-an-ti-CD19（Fab）-LDP had remarkable affinity with lym-phoma Raji cells;Raji lymphoma xenograft model was＆amp;nbsp;established successfully in nude mice and in vivo fluo-rescence imaging analysis indicated that the antibody-drug conjugates could specially be localized in the tar-get tumor.Conclusion The experiments in vivo and vitro confirm that anti-CD19 （Fab）-LDP has remarka-ble affinity to targeting CD19 ＋lymphoma cells,and the antibody drugs anti-CD19 （Fab ）-LDP have the probability to be new drugs for the treatment of malig-nant lymphoma.

关 键 词：淋巴瘤 anti-CD19(Fab) LDP Cy5标记 移植瘤模型 靶向分布 

分 类 号：R332[医药卫生—人体生理学] R392.11[医药卫生—基础医学]