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    • 4. 发明申请
    • METHODS TO TREAT DISEASE STATES BY INFLUENCING THE SIGNALING OF OX40-RECEPTORS AND HIGH THROUGHPUT SCREENING METHODS FOR IDENTIFYING SUBSTANCES THEREFOR
    • 通过影响OX40-受体的信号传导和高通量筛选方法来鉴定疾病的方法来治疗疾病状态
    • WO2007084559A3
    • 2007-11-22
    • PCT/US2007001228
    • 2007-01-16
    • UNIV TEXASLIU YONG-JUNITO TOMOKI
    • LIU YONG-JUNITO TOMOKI
    • C07K14/00A61K39/395
    • A61K38/177C07K16/2878G01N33/505G01N33/56972G01N2333/5428
    • OX40L inhibits the generation of IL-10-producing Tr1 cells from naïve and memory CD4+ T cells induced by the immunosuppressive 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.
    • OX40L抑制由免疫抑制药物地塞米松和维生素D3诱导的幼稚和记忆CD4 + T细胞产生IL-10的Tr1细胞。 OX40L的这种独特功能不被其他两种共刺激性TNF家族成员GITR配体和4-1BB配体共享。 OX40L还强烈抑制由诱导型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细胞的生成,并抑制调节性T细胞产生IL-10。 因此已经表明,通过单克隆抗体,小分子或OX40L信号通知人T细胞上的OX40-受体调节产生免疫抑制性T细胞的IL-10的产生和功能。 还提供了用于鉴定促进或抑制产生IL-10的T细胞的产生和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,例如人过敏性,自身免疫性和自身免疫性疾病以及癌症。
    • 5. 发明申请
    • METHODS TO TREAT DISEASE STATES BY INFLUENCING THE SIGNALING OF OX40-RECEPTORS AND HIGH THROUGHPUT SCREENING METHODS FOR IDENTIFYING SUBSTANCES THEREFOR
    • 通过影响OX40受体信号和高通量筛选方法治疗疾病的方法,用于鉴定其物质
    • WO2007084559A2
    • 2007-07-26
    • PCT/US2007/001228
    • 2007-01-16
    • BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEMLIU, Yong-JunITO, Tomoki
    • LIU, Yong-JunITO, Tomoki
    • A61K38/19
    • A61K38/177C07K16/2878G01N33/505G01N33/56972G01N2333/5428
    • OX40L inhibits the generation of IL-10-producing Tr1 cells from naïve and memory CD4+ T cells induced by the immunosuppressive 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.
    • 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疾病和癌症。