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    Methods to Treat Disease States by Influencing the Signaling of Ox-40-Receptors and High Throughput Screening Methods for Identifying Substances Therefor
    29.
    发明申请
    Methods to Treat Disease States by Influencing the Signaling of Ox-40-Receptors and High Throughput Screening Methods for Identifying Substances Therefor 审中-公开
    通过影响Ox-40受体信号治疗疾病状态的方法和高通量筛选方法鉴定其物质

    公开(公告)号：US20080286286A1

    公开(公告)日：2008-11-20

    申请号：US11659266

    申请日：2007-01-16

    申请人： Yong-Jun Liu ,  Tomoki Ito

    发明人： Yong-Jun Liu ,  Tomoki Ito

    IPC分类号： A61K39/395 ,  G01N33/535 ,  A61P37/02

    CPC分类号： A61K38/177 ,  C07K16/2878 ,  G01N33/505 ,  G01N33/56972 ,  G01N2333/5428

    摘要： OX40L inhibits the generation of IL-10-producing Tr1 cells from naïve and memory CD4+ T cells induced by the immunuosuppressive drugs dexamethasone and vitamin D3. This unique function of OX40L is not shared by two other costimulatory TNF-family members, GITR-ligand and 4-1BB-ligand. OX40L also strongly inhibits the generation of IL-10-producing Tr1 cells induced by two physiological stimuli provided by inducible costimulatory ligand and immature DCs and inhibits the production of IL-10 by regulatory T cells. It has thus been shown that signaling the OX40-receptor on human T cells by monoclonal antibodies, small molecules, or OX40L regulates the generation and function of IL-10 producing immunosuppressive T cells. Also provided are high throughput methods for identifying substances that promote or inhibit the generation and function of IL-10 producing T cells. Numerous disease states, such as human allergic, autoimmune, and autoimmune diseases, and cancer, may be treated by targeting OX40/OX40L.

    摘要翻译： OX40L抑制由免疫抑制药物地塞米松和维生素D3诱导的初始和记忆的CD4 + T细胞产生产生IL-10的Tr1细胞。 OX40L的这种独特功能不是由另外两种共刺激的TNF-家族成员，GITR-配体和4-1BB-配体共享。 OX40L还强烈地抑制由诱导性共刺激配体和未成熟DC提供的两种生理刺激诱导的产生IL-10的Tr1细胞的产生，并通过调节性T细胞抑制IL-10的产生。 因此，已经表明，通过单克隆抗体，小分子或OX40L信号传导人T细胞上的OX40-受体调节产生IL-10的免疫抑制性T细胞的产生和功能。 还提供了用于鉴定促进或抑制产生IL-10和产生T细胞的功能的物质的高通量方法。 可以通过靶向OX40 / OX40L来治疗许多疾病状态，例如人类过敏，自身免疫和自身免疫性疾病和癌症。