Direct in vivo gene transfer and expression in malignant cells using adenovirus vectors Academic Article uri icon

Overview

MeSH Major

  • 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.

publication date

  • April 1994

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 7519451

Additional Document Info

start page

  • 437

end page

  • 47

volume

  • 5

number

  • 4