title: High levels of gene transduction in human lung tumors following intralesional injection of recombinant adenovirus.
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.
authors.affiliation: Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Cusack
authors.forename: F R
authors.initials: FR
authors.lastname: Spitz
authors.forename: D
authors.initials: D
authors.lastname: Nguyen
authors.forename: W W
authors.initials: WW
authors.lastname: Zhang
authors.forename: R J
authors.initials: RJ
authors.lastname: Cristiano
authors.forename: J A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000472:pathogenicity; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000473:pathology; D003673:Defective Viruses / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D015552:Injections, Intralesional; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D011995:Recombination, Genetic; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001616:beta-Galactosidase