聚乙二醇修饰的肿瘤坏死因子-α对肿瘤坏死因子耐药肿瘤的体内抗肿瘤疗效
In vivo anti-tumor efficacy of polyethylene glycol-modified tumor necrosis factor-alpha against tumor necrosis factor-resistant tumors.
作者信息
Tsutsumi Y, Tsunoda S, Kaneda Y, Kamada H, Kihira T, Nakagawa S, Yamamoto Y, Horisawa Y, Mayumi T
机构信息
Faculty and Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
出版信息
Jpn J Cancer Res. 1996 Oct;87(10):1078-85. doi: 10.1111/j.1349-7006.1996.tb03113.x.
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.
我们之前报道过，最佳聚乙二醇化的肿瘤坏死因子-α（MPEG-TNF-α），其中56%的TNF-α赖氨酸氨基与聚乙二醇（PEG）偶联，其抗肿瘤效果比天然TNF-α大约强100倍。在此，我们评估了MPEG-TNF-α作为一种全身抗肿瘤治疗药物的有效性，使用B16-BL6黑色素瘤和结肠-26腺癌，据报道这两种肿瘤在体内对TNF-α具有抗性，与Meth-A纤维肉瘤相比。MPEG-TNF-α显著抑制了两种肿瘤的生长，且未引起任何TNF-α介导的副作用，而天然TNF-α没有抗肿瘤作用并引起了不良副作用。此外，MPEG-TNF-α极大地抑制了B16-BL6黑色素瘤的转移菌落形成。因此，MPEG-TNF-α可能是一种潜在的全身抗肿瘤治疗剂。
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