Thom A K, Fraker D L, Taubenberger J K, Norton J A
Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Surg Oncol. 1992 Aug;1(4):291-8. doi: 10.1016/0960-7404(92)90090-8.
Systemically administered tumour necrosis factor (TNF) has anti-tumour effects in animal tumour models but its clinical application is limited by severe toxicity. Interferon-gamma(IFN-gamma) has been shown to augment the anti-tumour effect of TNF. We evaluated the effect of paralesional (p.I.) injections of TNF plus IFN-gamma in a murine tumour model and compared the toxicity and anti-tumour effect with that seen with systemic administration. C57BL6 mice with 10-day subcutaneous MCA sarcomas were treated with daily p.I. injections of recombinant huTNF +/- IFN-gamma for 5 days. Optimal mean survival and 30-day cure rate was seen with doses of 5 micrograms TNF-alpha + 5000 U IFN-gamma (P < 0.05 vs. control or IFN-gamma alone). Tumour response after a single i.v. injection of 0-15 micrograms TNF + 5000 U IFN-gamma was then compared with five daily p.I. injections of the same dose of TNF-alpha and IFN-gamma. All animals with p.I. injections of > 5 micrograms TNF had initial complete necrosis of tumour with a variable degree of surrounding tissue necrosis, with rapid regrowth of tumour seen in some animals. Although treatment-related mortality was similar between i.v. and p.I. therapy, there was a higher percentage of animals cured with p.I. injections with overall cure rates in treated animals at 30 days of 17% vs. 72% (i.v. vs. p.I., P < 0.01) and 13% vs. 67% (P < 0.04) in a repeat study. 2+ clinical applications.
全身给药的肿瘤坏死因子（TNF）在动物肿瘤模型中具有抗肿瘤作用，但其临床应用因严重毒性而受到限制。γ干扰素（IFN-γ）已被证明可增强TNF的抗肿瘤作用。我们评估了在小鼠肿瘤模型中瘤旁（p.I.）注射TNF加IFN-γ的效果，并将其毒性和抗肿瘤作用与全身给药的情况进行了比较。对患有10日龄皮下MCA肉瘤的C57BL6小鼠，每天进行瘤旁注射重组人TNF +/- IFN-γ，持续5天。当剂量为5微克TNF-α + 5000 U IFN-γ时，观察到最佳平均生存期和30天治愈率（与对照组或单独使用IFN-γ相比，P < 0.05）。然后将单次静脉注射0 - 15微克TNF + 5000 U IFN-γ后的肿瘤反应与相同剂量的TNF-α和IFN-γ每天瘤旁注射5次的情况进行比较。所有瘤旁注射> 5微克TNF的动物，肿瘤最初均出现完全坏死，周围组织有不同程度的坏死，部分动物可见肿瘤快速再生。尽管静脉注射和瘤旁治疗的与治疗相关的死亡率相似，但瘤旁注射治愈的动物百分比更高，在重复研究中，治疗动物在30天时的总体治愈率分别为17%（静脉注射）对72%（瘤旁注射，P < 0.01）和13%对67%（P < 0.04）。2 +临床应用 。 （最后“2+ clinical applications”表述不太清晰准确，译文尽量按原文翻译）
