A novel antibody targeting CD24 and hepatocellular carcinoma in vivo by near-infrared fluorescence imaging

被引:38
作者
He, Hua [1 ]
Tu, Xiaojie [1 ]
Zhang, Juan [1 ]
Acheampong, Desmond Omane [1 ]
Ding, Li [1 ]
Ma, Zhaoxiong [1 ]
Ren, Xueyan [1 ]
Luo, Chen [1 ]
Chen, Zhiguo [1 ]
Wang, Tong [1 ]
Xie, Wei [1 ]
Wang, Min [1 ]
机构
[1] China Pharmaceut Univ, State Key Lab Nat Med, Sch Life Sci & Technol, Nanjing 210009, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
CD24; Monoclonal antibody; scFv; Tumor targeting; Near-infrared fluorescence imaging; T-CELLS; EXPRESSION; VACCINE; THERAPEUTICS; PREDICTOR; PROGNOSIS; MARKER; DRIVE; GENE;
D O I
10.1016/j.imbio.2015.07.010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Liver cancer is one of the most common malignant cancers worldwide. The poor response of liver cancer to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies because of its potential efficiency. One promising target is cluster of differentiation 24 (CD24), which is known to beover-expressed on hepatocellular carcinoma (HCC), providing prospect for HCC targeted diagnosis and therapy. In this study we developed a novel CD24 targeted monoclonal antibody G7mAb based on hybridoma technology and then generated a single-chain antibodyfragment (scFv) G7S. Firstly, ELISA, western blot, and flow cytometry assays demonstrated specific binding of CD24 by G7mAb and G7S. Further, G7mAb was demonstrated to have similar binding capacity as ML5 (a commercial Anti-CD24 Mouse Antibody) inimmunohistochemical assay. Further more, a near-infrared fluorescent dye multiplex probe amplification (MPA) was conjugated to G7mAb and G7S to form G7mAb-MPA and G7S-MPA. The near-infrared fluorescence imaging revealed that G7mAb and G7S aggregate in CD24 + Huh7 hepatocellular carcinoma xenograft tissuevia specific binding to CD24 in vivo. In conclussion, G7mAb and G7S were tumor targeted therapeutic and diagnostic potentials in vitro and in vivo as anticipated. (C) 2015 Elsevier GmbH. All rights reserved.
引用
收藏
页码:1328 / 1336
页数:9
相关论文
共 32 条
[1]   Regression of established liver tumor induced by monoepitopic peptide-based immunotherapy [J].
Belnoue, E ;
Guettier, C ;
Kayibanda, M ;
Le Rond, S ;
Crain-Denoyelle, AM ;
Marchiol, C ;
Ziol, M ;
Fradelizi, D ;
Rénia, L ;
Viguier, M .
JOURNAL OF IMMUNOLOGY, 2004, 173 (08) :4882-4888
[2]   Progress on new vaccine strategies for the immunotherapy and prevention of cancer [J].
Berzofsky, JA ;
Terabe, M ;
Oh, SK ;
Belyakov, IM ;
Ahlers, JD ;
Janik, JE ;
Morris, JC .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (11) :1515-1525
[3]   Management of hepatoceullular carcinoma [J].
Bruix, J ;
Sherman, M .
HEPATOLOGY, 2005, 42 (05) :1208-1236
[4]   Spontaneous and vaccine induced AFP-specific T cell phenotypes in subjects with AFP-positive hepatocellular cancer [J].
Butterfield, Lisa H. ;
Ribas, Antoni ;
Potter, Douglas M. ;
Economou, James S. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2007, 56 (12) :1931-1943
[5]   Potent antibody therapeutics by design [J].
Carter, PJ .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (05) :343-357
[6]  
Deng J., 2012, BIOMED RES INT
[7]   Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].
El-Serag, Hashem B. ;
Rudolph, Lenhard .
GASTROENTEROLOGY, 2007, 132 (07) :2557-2576
[8]   Bright and stable near-infrared fluorescent protein for in vivo imaging [J].
Filonov, Grigory S. ;
Piatkevich, Kiryl D. ;
Ting, Li-Min ;
Zhang, Jinghang ;
Kim, Kami ;
Verkhusha, Vladislav V. .
NATURE BIOTECHNOLOGY, 2011, 29 (08) :757-U133
[9]   Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection [J].
Gao, Qiang ;
Qiu, Shuang-Jian ;
Fan, Jia ;
Zhou, Jian ;
Wang, Xiao-Ying ;
Xiao, Yong-Sheng ;
Xu, Yang ;
Li, Yi-Wei ;
Tang, Zhao-You .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (18) :2586-2593
[10]  
Gerber DE, 2008, AM FAM PHYSICIAN, V77, P311