Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity-on-Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF-based AcTakine targeted to CD13 enables selective activation of the tumor neovasculature without any detectable toxicity in vivo. Upregulation of adhesion markers supports enhanced T-cell infiltration leading to control or elimination of solid tumors by, respectively, CAR T cells or a combination therapy with CD8-targeted type I interferon AcTakine. Co-treatment with a CD13-targeted type II interferon AcTakine leads to very rapid destruction of the tumor neovasculature and complete regression of large, established tumors. As no tumor markers are needed, safe and efficacious elimination of a broad range of tumor types becomes feasible.

中文翻译：

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使用靶向新血管的肿瘤坏死因子为基础的疗法可安全根除大型已建立的肿瘤。

全身毒性严重限制了肿瘤坏死因子（TNF）作为抗癌剂的临床应用。目标活性细胞因子（AcTakines）是一类新型的免疫细胞因子，具有改善的治疗指数。靶向CD13的基于TNF的AcTakine能够选择性激活肿瘤新脉管系统，而在体内没有任何可检测到的毒性。粘附标志物的上调支持增强的T细胞浸润，导致分别通过CAR T细胞或CD8靶向的I型干扰素AcTakine的联合疗法控制或消除实体瘤。与靶向CD13的II型干扰素AcTakine共同治疗可导致肿瘤新血管的快速破坏，并完全消退已建立的大型肿瘤。由于不需要肿瘤标记物，