Antitumor effects of an engineered and energized fusion protein consisting of an anti-CD20 scFv fragment and lidamycin

作     者：FANG Hong MIAO QingFang ZHANG ShengHua CHENG Xin XIONG DongSheng ZHEN YongSu 

作者机构：Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Institute of Hematology & Hospital of Blood Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300020 China Cancer Institute & Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China 

基　　金：supported by the National High Technology Research and Development Program of China(Grant No. 2006AA02A255) the National Natural Science Foundation of China(Grant No. 30701029) the National Science and Technology Major Projects(Grant Nos.2009ZX09103-720 and 2010ZX09401-407) 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2011年第54卷第3期

页      码：255-262页

摘      要：Antibody-based fusion proteins are the next generation of antibody therapies for cancer and other ***20 antigen,which is overexpressed on cell membranes in nearly 95% of cases of B-cell Non-Hodgkin s Lymphoma,is an attractive target for the therapy of B-lymphoid *** (LDM) is a potent enediyne-containing antitumor antibiotic that now has entered phase II clinical *** this study,we prepared an engineered fusion protein,scFv-LDP,consisting of an anti-CD20 scFv fragment and the apoprotein LDP of LDM using DNA *** purification and refolding,scFv-LDP was found to bind specifically to CD20-positive lymphoma cells using ELISA and indirect immunofluorescent cytochemical staining *** energized fusion protein scFv-LDP-AE was obtained using molecular reconstitution of the active chromophore AE of LDM and *** assay revealed potent cytotoxicity of scFv-LDP-AE to CD20-positive Raji and Daudi cells,with IC 50 values of 1.21×10-11 and 6.24×10-11 mol L-1,*** in vivo subcutaneous xenograft model of CD20-positive B cell lymphoma in BALB/c (nu/nu) mice was also *** were given intravenously on day 14 and 21 after tumor *** terms of maximal tolerated doses,scFv-LDP-AE at 0.3 mg kg-1 suppressed tumor growth by 79.3%,and LDM at 0.05 mg kg-1 by 68.6% (P<0.05).Results suggested scFv-LDP-AE could be a potential candidate for tumor-targeting therapy.

主 题 词：抗肿瘤作用 单链抗体 融合蛋白 力达霉素 工程 组成 B细胞淋巴瘤 DNA重组 

学科分类：07[理学] 08[工学] 09[农学] 071007[071007] 071005[071005] 090102[090102] 0710[理学-生物科学类] 1007[医学-药学类] 0830[工学-生物工程类] 100705[100705] 0901[农学-植物生产类] 0836[0836] 10[医学] 

核心收录：

D　O　I：10.1007/s11427-011-4143-4

馆 藏 号：203318430...