Preclinical development of human granulocyte-macrophage colony-stimulating factor-transfected melanoma cell vaccine using established canine cell lines and normal dogs
| Autor: | Joseph K. Burkholder, G. S. Hogge, Ning-Sun Yang, J. Culp, E. G. MacEwen, R. R. Dubielzig, Mark R. Albertini |
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| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Genetic enhancement Enzyme-Linked Immunosorbent Assay Pilot Projects Transfection Cancer Vaccines Dogs Immune system Genes Reporter Tumor Cells Cultured Canine Melanoma medicine Animals Humans Intradermal injection Luciferases Melanoma Molecular Biology Cell Death Dose-Response Relationship Drug business.industry Gene Transfer Techniques Granulocyte-Macrophage Colony-Stimulating Factor Dose-Response Relationship Radiation beta-Galactosidase medicine.disease Eosinophils Granulocyte macrophage colony-stimulating factor Cell culture Cancer research Molecular Medicine business medicine.drug |
| Zdroj: | Cancer Gene Therapy. 6:26-36 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700015 |
| Popis: | Tumor vaccines and gene therapy have received significant attention as means of increasing cellular and humoral immune responses to cancer. We conducted a pilot study of seven research dogs to determine whether intradermal injection of canine tumor cells transfected via the Accell particle-mediated gene transfer device with the cDNA for human granulocyte-macrophage colony-stimulating factor (hGM-CSF) would generate biologically relevant levels of protein and result in demonstrable histological changes at sites of vaccination. Tumor cell vaccines of 10(7) irradiated canine melanoma cells were nontoxic, safe, and well tolerated. No significant alterations in blood chemistry values or hematological profiles were detected. A histological review of control vaccine sites revealed inflammatory responses predominated by eosinophils, whereas vaccine sites with hGM-CSF-transfected tumor cells had an influx of neutrophils and macrophages. Enzyme-linked immunosorbent assays of skin biopsies from vaccine sites had local hGM-CSF production (8.68-16.82 ng/site of injection) at 24 hours after injection and detectable levels (0.014-0.081 ng/site) for < or =2 weeks following vaccination. Flow cytometric analysis of hGM-CSF-transfected cells demonstrated < or =25% transfection efficiency, and hGM-CSF levels obtained during time-course assays demonstrated biologically relevant levels for both irradiated and nonirradiated samples. These data demonstrate the in vivo biological activity of irradiated hGM-CSF-transfected canine tumor cells and help provide evidence for a valid translational research model of spontaneous tumors. |
| Databáze: | OpenAIRE |
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