Synthekine Inc., 515 O'Brien Drive, Menlo Park, CA94025, Australia.
Semin Immunol. 2019 Aug;44:101325. doi: 10.1016/j.smim.2019.101325. Epub 2019 Nov 6.
The expansion and activation of tumor antigen reactive CD8 T cells are primary goals of immunotherapies for cancer. IL-10 is an anti-inflammatory cytokine with an essential role in the development and proliferation of regulatory T cells, restricting myeloid and chronic inflammatory T cell responses. However, IL-10 is also essential for the expansion of antigen activated, tumor specific CD8 T cells, leading to spontaneous tumor development in IL-10 deficient patients and mice. IL-10 induces IFNγ and cytotoxic mediators in antigen activated T cells. In clinical trials, monotherapy with recombinant, pegylated IL-10 (Pegilodecakin) induced objective responses in cancer patients. Patients receiving pegilodecakin had a systemic increase of IFNγ and granzymes, proliferation and expansion of immune checkpoint positive CD8 T cells. Combination of pegilodecakin with anti-PD-1 appeared to improve on the efficacy of the single agents.
肿瘤抗原反应性 CD8 T 细胞的扩增和激活是癌症免疫疗法的主要目标。IL-10 是一种抗炎细胞因子，在调节性 T 细胞的发育和增殖中具有重要作用，限制髓样和慢性炎症性 T 细胞反应。然而，IL-10 对于抗原激活的、肿瘤特异性 CD8 T 细胞的扩增也是必不可少的，导致 IL-10 缺陷患者和小鼠自发发生肿瘤。IL-10 诱导抗原激活的 T 细胞中 IFNγ 和细胞毒性介质的产生。在临床试验中，重组聚乙二醇化 IL-10（Pegilodecakin）单药治疗可诱导癌症患者出现客观反应。接受 Pegilodecakin 治疗的患者体内 IFNγ 和颗粒酶增加，免疫检查点阳性 CD8 T 细胞增殖和扩增。Pegilodecakin 与抗 PD-1 联合使用似乎提高了单药治疗的疗效。
