期刊
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
卷 143, 期 10, 页码 1929-1940出版社
SPRINGER
DOI: 10.1007/s00432-017-2436-0
关键词
CD24; Antibody-drug conjugates (ADCs); Doxorubicin (DOX); G7mAb; Hepatocellular carcinoma
类别
资金
- National Natural Science Foundation of China [NSFC81273425, NSFC81473125]
- Natural Science Foundation of Jiangsu Province [BK20161459]
- Jiangsu Province Qinglan Project
- Priority Academic Program Development Innovation Program of Jiangsu Higher Education Institutions
- Graduate Student Innovation Project - Zhejiang Huahai Pharmaceutical Co [1010040003]
- Graduate Innovation Program of Jiangsu Province [KYLX15_0670]
- Undergraduate Training Program of Jiangsu Province for Innovation and Entrepreneurship [SY15090]
Purpose Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for clinical application. Cluster of differentiation 24 (CD24) is over-expressed in several human malignancies, especially in hepatocellular carcinoma (HCC). We aimed to develop a new class of CD24-targeted ADCs for HCC. Methods DOX was conjugated with G7mAb by a heterobifunctional cross-linker GMBS (N-[gamma-maleimido butyryloxy] succinimide ester) and further analyzed using HPLC. The targeting specificity and endocytosis of the newly generated ADC, G7mAb-DOX, were characterized using flow cytometry assay, near-infrared fluorescence imaging and laser scanning confocal microscope. The antitumor effects were evaluated in nude mice bearing HCC xenografts. Results G7mAb-DOX with average two drug molecules per antibody was selectively captured and endocytosed by CD24 (+) tumor cells in vitro. In vivo, the ADC was proved to target tumor tissues, suppress tumor growth and prolong the survival of HCC-bearing nude mice with improved efficacy and less systemic toxicity compared with either G7mAb or DOX single-agent treatment. Conclusions These studies provide proof of concept for development of DOX-based ADCs which provide a novel approach for HCC-targeted immune therapy in clinical application.
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