RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Engineering IL-2 for immunotherapy of autoimmunity and cancer.
Engineering IL-2 for immunotherapy of autoimmunity and cancer.
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IL-2 的 T 细胞生长因子活性的临床前研究使该细胞因子成为近 30 年前首个获美国食品药品监督管理局批准用于治疗癌症的免疫疗法。此后,我们认识到 IL-2 除了通过作用于效应 T 细胞和记忆 T 细胞来促进免疫外,还通过调节性 T 细胞(T reg 细胞)在调节耐受中发挥重要作用。IL-2 研究史上的另一个关键事件是解析了 IL-2 与其三联受体结合的晶体结构,这推动了细胞类型选择性工程化 IL-2 产品的开发。这些新的 IL-2 类似物靶向 T reg 细胞以对抗自身免疫和炎症性疾病背景下失调的免疫系统,或靶向效应 T 细胞、记忆 T 细胞和NK 细胞以增强其抗肿瘤反应。IL-2 生物制剂已在临床前研究中证明有效,其中一些的临床评估目前正在进行中。这些研究将很快揭示工程化 IL-2 生物制剂是否真正能够利用 IL-2-IL-2 受体通路作为自身免疫和癌症的有效单一疗法或联合疗法。
Preclinical studies of the T cell growth factor activity of IL-2 resulted in this cytokine becoming the first immunotherapy to be approved nearly 30 years ago by the US Food and Drug Administration for the treatment of cancer. Since then, we have learnt the important role of IL-2 in regulating tolerance through regulatory T cells (T reg cells) besides promoting immunity through its action on effector T cells and memory T cells. Another pivotal event in the history of IL-2 research was solving the crystal structure of IL-2 bound to its tripartite receptor, which spurred the development of cell type-selective engineered IL-2 products.
These new IL-2 analogues target T reg cells to counteract the dysregulated immune system in the context of autoimmunity and inflammatory disorders or target effector T cells, memory T cells and natural killer cells to enhance their antitumour responses.
IL-2 biologics have proven to be effective in preclinical studies and clinical assessment of some is now underway. These studies will soon reveal whether engineered IL-2 biologics are truly capable of harnessing the IL-2-IL-2 receptor pathway as effective monotherapies or combination therapies for autoimmunity and cancer.
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