Targeting a Recombinant Adenovirus Vector to HCC Cells Using a Bifunctional Fab-Antibody Conjugate

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• 作者：Yoon ; Seung-Kew ; Mohr ; Leonhard ; O'Riordan ; Catherine R. ; Lachapelle ; Amy ; Armentano ; Donna ; et. al.
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2000
• 出版时间：June 7, 2000
• 年：2000
• 卷：272
• 期：2
• 页码：497-504
• 全文大小：320 K

文摘

We developed a specific adenoviral gene delivery system with monoclonal antibody (mAb) AF-20 that binds to a 180 kDa antigen highly expressed on human hepatocellular carcinoma (HCC) cells. A bifunctional Fab-antibody conjugate (2Hx-2-AF-20) was generated through AF-20 mAb crosslinkage to an anti-hexon antibody Fab fragment. Uptake of adenoviral particles and gene expression was examined in FOCUS HCC and NIH 3T3 cells by immunofluorescence; β-galactosidase expression levels were determined following competitive inhibition of adenoviral CAR receptor by excess fibre knob protein. The chimeric complex was rapidly internalized at 37°C, and enhanced levels of reporter gene expression was observed in AF-20 antigen positive HCC cells, but not in AF-20 antigen negative NIH 3T3 control cells. Targeting of recombinant adenoviral vectors to a tumor associated antigen by a bifunctional Fab-antibody conjugate is a promising approach to enhance specificity and efficiency of gene delivery to HCC.