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In-Vitro Internalization and In-Vivo Tumor Uptake of Anti-EGFR Monoclonal Antibody LA22 in A549 Lung Cancer Cells and Animal Model
Liu, Zhaofei1; Yu, Zilin1; He, Weiwei1; Ma, Shujun2; Sun, Le2; Wang, Fan1
关键词Epidermal Growth Factor Receptor (Egfr) Monoclonal Antibody La22 Internalization Immunoscintigraphy Tumor Targeting
刊名CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
2009-02-01
DOI10.1089/cbr.2008.0537
24期:1页:15-23
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Medicine, Research & Experimental ; Pharmacology & Pharmacy ; Radiology, Nuclear Medicine & Medical Imaging
资助者Beijing Science and Technology Program ; 863 Project ; Beijing Science and Technology Program ; 863 Project
研究领域[WOS]Oncology ; Research & Experimental Medicine ; Pharmacology & Pharmacy ; Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]GROWTH-FACTOR RECEPTOR ; EXPRESSION ; THERAPY ; BINDING ; XENOGRAFTS ; RETENTION ; MOLECULE ; TOXIN
英文摘要

Purpose: Internalization is one of the key steps for anticancer immunoconjugates to deliver the drugs inside of cancer cells. Herein, the internalization property of antiepidermal growth factor receptor (EGFR) monoclonal antibody (mAb) LA22 was evaluated. Materials and Methods: The binding and internalization properties of LA22 on A549 cells were investigated by using (125)I-LA22. In vitro internalization was also confirmed by indirect fluorescent staining. In vivo tumor targeting and internalization of (125)I-LA22 were evaluated in the A549 nucle mice model. Results: The mAb LA22 showed a high affinity to EGFRs expressed on A549 cells (Kd = 0.69 +/- 0.13 nM). The in vitro internalization of LA22 was time- and temperature dependent. The cell-surface-bound LA22 was rapidly internalized at 37 degrees C. The experimental results of LA22 internalization obtained from radioassay and fluorescent staining were consistent with a good linear correlation. At 72 hours postinjection, a clear gamma-image of tumor was obtain in A549 tumor xenografts, and the tumor uptake of (125)I-LA22 was 8.00 +/- 0.61 percent injected dose per gram (%ID/g) (2.19 +/- 0.37 %ID/g for (125)I-mIgG). Similar to the in vitro observation, 64.06% of the cell-bound mAb LA22 was internalized into the tumor cells in vivo. Conclusions: The mAb, LA22, is a rapid, high-internalizing antibody, and this property makes it a promising vehicle for tumor-targeted drug delivery.

语种英语
所属项目编号Z00004105040311 ; D0206001041991 ; 2007AA02Z467
资助者Beijing Science and Technology Program ; 863 Project ; Beijing Science and Technology Program ; 863 Project
WOS记录号WOS:000263898300003
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54845
专题北京大学医药卫生分析中心
作者单位1.Welson Pharmaceut Inc, Ellicott City, MD USA
2.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Liu, Zhaofei,Yu, Zilin,He, Weiwei,et al. In-Vitro Internalization and In-Vivo Tumor Uptake of Anti-EGFR Monoclonal Antibody LA22 in A549 Lung Cancer Cells and Animal Model[J]. CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS,2009,24(1):15-23.
APA Liu, Zhaofei,Yu, Zilin,He, Weiwei,Ma, Shujun,Sun, Le,&Wang, Fan.(2009).In-Vitro Internalization and In-Vivo Tumor Uptake of Anti-EGFR Monoclonal Antibody LA22 in A549 Lung Cancer Cells and Animal Model.CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS,24(1),15-23.
MLA Liu, Zhaofei,et al."In-Vitro Internalization and In-Vivo Tumor Uptake of Anti-EGFR Monoclonal Antibody LA22 in A549 Lung Cancer Cells and Animal Model".CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS 24.1(2009):15-23.
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