High levels of gene transduction in human lung tumors following intralesional injection of recombinant adenovirus

Cancer Gene Ther. Jul-Aug 1996;3(4):245-9.

Abstract

To effect gene transfer into large solid malignancies for the purpose of clinical application, new treatment strategies using intralesional administration of adenovirus were studied. Replication-deficient adenovirus Ad5LacZ, containing the Escherichia coli beta-galactosidase (beta-gal) gene (LacZ), was injected directly into 1-cm x 1-cm subcutaneous xenograph tumors of human large cell lung cancers (H460 and H1299). Each tumor received a single injection or three injections of purified virus, diluted in 200 microL of phosphate-buffered saline. The tumors were harvested 3 days after the last injection, serially sectioned, and stained with X-gal. The cells expressing beta-gal were counted by using digital image analysis and the percentage of tumor cells transduced was calculated. After a single viral injection of 1 x 10(9) PFU, 5 x 10(9) PFU, or 1 x 10(10) PFU solid tumor transduction increased significantly with dose escalation. At a dose of 1 x 10(10) PFU, transduction of the H1299 and H460 tumors was 80.2% and 46.7%, respectively. Dividing the viral dose into three injections given on alternating days had no significant effect on viral transduction. These data demonstrate that a large portion of an established human lung cancer cell line tumor undergoes gene transduction after a single intralesional injection of recombinant adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / pathogenicity
  • Carcinoma, Large Cell / genetics*
  • Carcinoma, Large Cell / pathology
  • Defective Viruses / genetics
  • Defective Viruses / pathogenicity
  • Humans
  • Injections, Intralesional
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Recombination, Genetic
  • Transduction, Genetic*
  • Tumor Cells, Cultured
  • beta-Galactosidase / genetics

Substances

  • beta-Galactosidase