Abstract
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. (C) 2000 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 497-504 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 272 |
| Issue number | 2 |
| DOIs | |
| State | Published - 7 Jun 2000 |
Bibliographical note
Funding Information:This work was supported in part by Grants CA35711 and AA-08169 from the National Institutes of Health, a Grant from Genzyme Corporation, and by Grant Mo 699/2-2 from the Deutsche Forschun-gsgemeischaft, Bonn, Germany (to L.M.). S.-K. Yoon is the recipient of a grant from the Korea Science and Engineering Foundation (KOSEF). The authors gratefully acknowledge support from the NSF Biotechnology Process Engineering Center, Massachusetts Institute of Technology. The authors thank Mrs. Sharon Chiott for editorial assistance in the completion of this manuscript.
Keywords
- Adenovirus
- Human hepatocellular carcinoma
- Monoclonal antibody
- Targeting