Intranasal therapy with an adenoviral vector containing the murine interleukin-12 gene eradicates osteosarcoma lung metastases.
The purpose of these studies was to determine the effect of adenovirus-mediated interleukin-12 (IL-12) gene transfer on the growth and development of osteosarcoma (OS) lung metastases in nude mice. A nude mouse model was produced by repetitive cycling of human SAOS OS cells through the lung. The resultant SAOS-LM6 cell line produced microscopic lung metastases by 5-6 weeks after i.v. injection of the tumor cells, with visible lung metastases present 8 weeks after injection. Transfection of SAOS-LM6 cells with a plasmid containing the murine IL-12 gene resulted in a decrease in metastatic potential. Animals injected with IL-12-transfected clones had fewer metastases compared with mice injected with SAOS-LM6 cells transfected with a control plasmid. Furthermore, nasal delivery of an adenoviral vector containing the murine IL-12 gene resulted in the inhibition of pulmonary metastases. Together, these data indicate that IL-12 may be an effective agent against OS and that nasal delivery may offer a unique way to deliver the gene to the local tumor environment, potentially decreasing systemic toxic effects.
Worth
L L
LL
Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Jia
S F
SF
Zhou
Z
Z
Chen
L
L
Kleinerman
E S
ES
D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000628:therapy; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D018664:Interleukin-12; D007371:Interferon-gamma