In vivo anti-tumor efficacy of polyethylene glycol-modified tumor necrosis factor-alpha against tumor necrosis factor-resistant tumors.
We previously reported that the optimally PEGylated tumor necrosis factor-alpha (MPEG-TNF-alpha), in which 56% of the TNF-alpha-lysine amino groups were coupled with polyethylene glycol (PEG), had about 100-fold greater anti-tumor effect than native TNF-alpha. Here, we assessed the usefulness of MPEG-TNF-alpha as a systemic anti-tumor therapeutic drug, using B16-BL6 melanoma and colon-26 adenocarcinoma, which have been reported to be resistant to TNF-alpha in vivo, as compared with Meth-A fibrosarcoma. MPEG-TNF-alpha markedly inhibited the growth of both tumors without causing any TNF-alpha-mediated side-effects, whereas native TNF-alpha had no anti-tumor effects and caused adverse side-effects. In addition, MPEG-TNF-alpha drastically inhibited the metastatic colony formation of B16-BL6 melanoma. MPEG-TNF-alpha may, thus, be a potential systemic anti-tumor therapeutic agent.
Tsutsumi
Y
Y
Faculty and Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Tsunoda
S
S
Kaneda
Y
Y
Kamada
H
H
Kihira
T
T
Nakagawa
S
S
Yamamoto
Y
Y
Horisawa
Y
Y
Mayumi
T
T
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols