Tumor necrosis factor (TNF) was discovered in 1975 as a lipopolysaccharide-induced serum factor that causes necrosis of tumors (Carswell et al, 1975). It was later found that TNF and cachectin, a factor causing wasting disease, were one and the same molecule (Beutler et al, 1985). Studies on the inflammatory activity of TNF have been translated into clinical success, namely blocking antibodies used to suppress autoimmune diseases. Research on TNF anti-tumor activity, in contrast, has not yet resulted in a therapeutic breakthrough. This may change, based on a study by Huyghe et al (2020) describing novel "designer cytokines" (TNF and interferon-γ) that increase local activity by targeting the CD13-positive tumor vasculature, while simultaneously lowering the binding affinity to the respective cytokine receptor, thereby reducing off-target effects on normal cells.

中文翻译：

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针对肿瘤脉管系统的“设计细胞因子”认为全局且局部起作用。

肿瘤坏死因子（TNF）于1975年被发现是一种脂多糖诱导的血清因子，可导致肿瘤坏死（Carswell等，1975）。后来发现，TNF和恶病质，一种导致疾病消瘦的因子，是同一分子（Beutler等，1985）。关于TNF的炎性活性的研究已经转化为临床成功，即阻断用于抑制自身免疫疾病的抗体。相比之下，TNF抗肿瘤活性的研究尚未取得治疗突破。基于Huyghe等人（2020）的一项研究，该研究可能会改变，这种新的“设计细胞因子”（TNF和干扰素-γ）通过靶向CD13阳性肿瘤脉管系统增加局部活性，同时降低了对各自的结合亲和力细胞因子受体