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Model Characteristics - Model:
Intravenous administration of polyethylene glycol-modified tumor
necrosis factor-α completely regressed solid tumor in Meth-A murine sarcoma model
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| Model Descriptor |
Intravenous administration of polyethylene glycol-modified tumor
necrosis factor-α completely regressed solid tumor in Meth-A murine sarcoma model
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| Official Nomenclature |
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
BALB/c
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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 |
The systemic administration of TNF-¿ often induces toxic side effects. Thus, cancer therapy with TNF-¿ has been limited to local intratumoral administration. We previously reported that the chemical modification of TNF-¿ with polyethylene glycol (PEG) prolonged its plasma half-life, and increased its anti-tumor activiy in the Meth-A murine solid tumor model. MPEG-TNF-¿, in which 56% of the lysine-amino groups of TNF-a were coupled with PEG, was 100-fold more potent as an anti-tumor agent than native TNF-¿, so that the therapeutic dose of TNF-¿ could be decreased, resulting in a decrease in the side effects. Here we attempt to regress completely Meth-A solid tumor in mice by plural i.v. administration of MPEG-TNF-¿ alone.
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| Phenotype |
Complete regression of solid tumors was achieved by plural intravenous (i.v.) administrations of polyethylene glycol (PEG)-modified tumor necrosis factor-α (TNF-α), prepared by covalently modifying natural human TNF-α with N-succinimidyl succinate PEG. The anti-tumor efficacy of PEG-modified TNF-α (MPEG-TNF-α) was compared with that of native TNF-α in the Meth-A murine fibrosarcoma model. MPEG-TNF-α and native TNF-α were given as i.v. injections twice a week for 2 weeks. The anti-tumor activity of MPEG-TNF-α was dose-dependent and was far superior to that of native TNF-α. Complete regression was observed in 3 of the 8 mice administered native TNF-α at the dose of 10,000 JRU (Japan reference unit), but 4 of the 5 remaining mice died during the therapeutic period. At 5,000 JRU of native TNF-α, no case of complete regression was observed. By contrast, complete regression was obtained in all 10 mice given 200 JRU of MPEG-TNF-α. No side-effects were observed at the dose of 500 JRU of MPEG-TNF-α, which was 2.5 times the minimal dose (200 JRU) of MPEG-TNF-α required for complete regression in all treated mice. MPEG-TNF-α appears to have potential as a candidate anti-tumor therapeutic agent.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
Female Only
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| Submitted by |
caMOD, Curator
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| Principal Investigator / Lab |
Mayumi*, Tadanori
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| Comment |
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| Model Availability: This model is available from |
| Strain |
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