Direct in vivo gene transfer and expression in malignant cells using adenovirus vectors.
| Publication Type | Academic Article |
| Authors | Brody S, Jaffe H, Han S, Wersto R, Crystal R |
| Journal | Hum Gene Ther |
| Volume | 5 |
| Issue | 4 |
| Pagination | 437-47 |
| Date Published | 04/01/1994 |
| ISSN | 1043-0342 |
| Keywords | Adenoviruses, Human, Defective Viruses, Gene Expression Regulation, Neoplastic, Gene Transfer Techniques, Genetic Vectors, Membrane Proteins, Mesothelioma, Recombinant Fusion Proteins, alpha 1-Antitrypsin, beta-Galactosidase |
| Abstract | To evaluate the ability of replication-deficient, recombinant adenovirus vectors to transfer genes to human tumor cells in vivo, adenovirus vectors containing the Escherichia coli lacZ (Ad.RSV beta gal) gene (coding for beta-galactosidase; used as a cell marker for gene transfer) or the human alpha 1-antitrypsin (Ad-alpha 1AT) cDNA (used as an example of a secreted protein) were administered intraperitoneally to nude mice with human malignant mesothelioma cell (H-MESO-1) malignant ascites. Preliminary in vitro studies showed that both vectors effectively transferred genes to H-MESO-1 cells. Tumor cells recovered from ascites of animals intraperitoneally administered a control adenovirus revealed no evidence of beta-galactosidase (beta-gal) activity 3 or 14 days later. In contrast, beta-gal activity was detected at the same time points in tumor cells from animals receiving intraperitoneal Ad.RSV beta gal. Flow cytometric quantification of beta-gal activity in recovered cells showed < 3% beta-gal-positive cells in animals administered control virus, but in animals administered intraperitoneal Ad.RSV beta gal there was a mean of 71 +/- 18% positive cells at 3 days and 56 +/- 27% at 14 days. Human alpha 1AT was not detected by enzyme-linked immunosorbent assay (ELISA) in ascites of animals receiving a control virus; however, in ascites of animals administered Ad-alpha 1AT, 21,000 +/- 3,800 ng/ml of human alpha 1AT was detected at 3 days and 4,900 +/- 1,700 ng/ml at 14 days. These data demonstrate that replication-deficient recombinant adenovirus vectors can be used to transfer genes to malignant cells in vivo and suggest a new strategy for genetic modification for antitumor therapy. |
| DOI | 10.1089/hum.1994.5.4-437 |
| PubMed ID | 7519451 |