In vivoAnti-tumor Efficacy of Polyethylene Glycol-modified Tumor Necrosis Factor-α against Tumor Necrosis Factor-resistant Tumors

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Abstract
We previously reported that the optimally PEGylated tumor necrosis factor‐α (MPEG‐TNF‐α), in which 56% of the TNF‐α‐lysine amino groups were coupled with polyethylene glycol (PEG), had about 100‐fold greater anti‐tumor effect than native TNF‐α. Here, we assessed the usefulness of MPEG‐TNF‐α as a systemic anti‐tumor therapeutic drug, using B16‐BL6 melanoma and colon‐26 adenocarcinoma, which have been reported to be resistant to TNF‐αin vivo, as compared with Meth‐A fibrosarcoma. MPEG‐TNF‐α markedly inhibited the growth of both tumors without causing any TNF‐α‐mediated side‐effects, whereas native TNF‐α had no anti‐tumor effects and caused adverse side‐effects. In addition, MPEG‐TNF‐α drastically inhibited the metastatic colony formation of B16‐BL6 melanoma. MPEG‐TNF‐α may, thus, be a potential systemic anti‐tumor therapeutic agent.

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