Intravenous administration of polyethylene glycol-modified tumor necrosis factor-α completely regressed solid tumor in Meth-A murine sarcoma model
Y. Tsutsumi, T. Kihira, S. Tsunoda, K. Kubo, M. Miyake, T. Kanamori, S. Nakagawa and T. MayumiJapanese Journal of Cancer Research (1994), Vol. 85 pages 1185-1188.
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), in which 56% of the TNF-α-lysine residues were coupled with PEG, 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.