Intravenous administration of polyethylene glycol-modified tumor necrosis factor-alpha completely regressed solid tumor in Meth-A murine sarcoma model

Jpn J Cancer Res. 1994 Dec;85(12):1185-8. doi: 10.1111/j.1349-7006.1994.tb02926.x.

Abstract

Complete regression of solid tumors was achieved by plural intravenous (i.v.) administrations of polyethylene glycol (PEG)-modified tumor necrosis factor-alpha (TNF-alpha), prepared by covalently modifying natural human TNF-alpha with N-succinimidyl succinate PEG. The anti-tumor efficacy of PEG-modified TNF-alpha (MPEG-TNF-alpha), in which 56% of the TNF-alpha-lysine residues were coupled with PEG, was compared with that of native TNF-alpha in the Meth-A murine fibrosarcoma model. MPEG-TNF-alpha and native TNF-alpha were given as i.v. injections twice a week for 2 weeks. The anti-tumor activity of MPEG-TNF-alpha was dose-dependent and was far superior to that of native TNF-alpha. Complete regression was observed in 3 of the 8 mice administered native TNF-alpha 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-alpha, no case of complete regression was observed. By contrast, complete regression was obtained in all 10 mice given 200 JRU of MPEG-TNF-alpha. No side-effects were observed at the dose of 500 JRU of MPEG-TNF-alpha, which was 2.5 times the minimal dose (200 JRU) of MPEG-TNF-alpha required for complete regression in all treated mice. MPEG-TNF-alpha appears to have potential as a candidate anti-tumor therapeutic agent.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Fibrosarcoma / drug therapy*
  • Histocompatibility Antigens
  • Injections, Intravenous
  • Mice
  • Neoplasm Transplantation
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use*
  • Remission Induction
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / therapeutic use*

Substances

  • Antigens, Neoplasm
  • Histocompatibility Antigens
  • PEG-modified tumor necrosis factor-alpha
  • Tumor Necrosis Factor-alpha
  • tumor-associated transplantation antigen
  • Polyethylene Glycols