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Model Characteristics - Model:
Preclinical investigation of PEGylated tumor necrosis factor alpha in dogs with spontaneous tumors
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| Model Descriptor |
Preclinical investigation of PEGylated tumor necrosis factor alpha in dogs with spontaneous tumors
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| Official Nomenclature |
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| Genotype |
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| Species |
Dog (Canis familiaris)
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| Strain |
Not specified
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| Is This a Tool Strain? |
No
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Developmental Stage
(applies only to Zebrafish) |
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| Experimental Design |
Tumor necrosis factor-alpha (TNF) is a cytokine with potent antitumor activity; however, toxicity and short half-life have limited its utility. Polyethylene glycol (PEG) conjugation of biotherapeutics can decrease immunogenicity while improving bioactivity and half-life. PEGylation of TNF (PEG-TNF) significantly improved half-life and toxicity in a href=http://cancermodels.nci.nih.gov/camod/ViewModelAction.do?unprotected_method=populateModelCharacteristics&aModelID=150066105 target="_blank" mice/a, resulting in enhanced antitumor activity. This study characterized toxicity, biological effect, and antitumor activity of PEG-TNF in pet dogs with spontaneous cancer. The laboratory dog is a common model for the study of the hemodynamic effects of TNF¿. Similar changes in blood pressure, cardiac output, and oxygenation are observed in dogs receiving hTNF¿ as are seen in humans, at doses below the predicted therapeutic range. In addition, hTNF¿ induces diverse molecular and biochemical events in dogs similar to those described in humans.
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| Phenotype |
Using a clinically relevant, spontaneous large animal model of neoplasia, we have shown that biologically effective doses of PEG-TNF can be administered safely, and that PEG-TNF administration is associated with encouraging biological activity. These results justify the clinical evaluation of PEG-TNF in human cancer.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
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| Submitted by |
caMOD, Curator
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| Principal Investigator / Lab |
Vail*, David M
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| Comment |
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| Model Availability: This model is available from |
| Strain |
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