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    • 3. 发明申请
    • COMPOSITIONS AND METHODS FOR THE TREATMENT OF IMMUNOLOGIC DISORDERS
    • 用于治疗免疫性疾病的组合物和方法
    • WO2008083169A2
    • 2008-07-10
    • PCT/US2007/088841
    • 2007-12-26
    • JOHNS HOPKINS UNIVERSITYCHEN, LiepingTAMADA, Koji
    • CHEN, LiepingTAMADA, Koji
    • C07K14/00
    • C07K16/00C07K16/2875C07K2317/73C07K2319/30
    • Compositions and methods for preventing, reducing or inhibiting immunologic disorders are provided. Suitable compositions include one or more LIGHT-HVEM antagonists. LIGHT-HVEM antagonists include compounds that inhibit, reduce, or block the biological activity or expression of LIGHT and/or HVEM. LIGHT-HVEM antagonists can reduce or inhibit the binding of LIGHT to HVEM, but do not significantly modulate the binding of LTβ to LTBR. Suitable compositions include antibodies and antibody fragments, decoy polypeptides, small molecule inhibitors and inhibitory nucleic acids. Methods for using LIGHT-HVEM antagonists to reduce or inhibit T cell activation and survival are also provided. Therapeutic uses for LIGHT-HVEM antagonists to prevent or treat immunologic diseases and disorders including graft rejection, graft-versus-host disease, inflammatory immune responses, and autoimmune disorders are provided.
    • 提供了用于预防,减少或抑制免疫疾病的组合物和方法。 合适的组合物包括一种或多种LIGHT-HVEM拮抗剂。 LIGHT-HVEM拮抗剂包括抑制,减少或阻断LIGHT和/或HVEM的生物学活性或表达的化合物。 LIGHT-HVEM拮抗剂可减少或抑制LIGHT与HVEM的结合,但不显着调节LTβ与LTBR的结合。 合适的组合物包括抗体和抗体片段,诱饵多肽,小分子抑制剂和抑制性核酸。 还提供了使用LIGHT-HVEM拮抗剂减少或抑制T细胞活化和存活的方法。 提供了用于LIGHT-HVEM拮抗剂预防或治疗免疫性疾病和病症的治疗用途,所述免疫性疾病和病症包括移植物排斥,移植物抗宿主病,炎症性免疫应答和自身免疫性疾病。
    • 7. 发明申请
    • B7-DC VARIANTS
    • B7-DC变量
    • WO2009029342A2
    • 2009-03-05
    • PCT/US2008/069819
    • 2008-07-11
    • THE JOHNS HOPKINS UNIVERSITYCHEN, Lieping
    • CHEN, Lieping
    • C07K14/705A61K38/17
    • C07K14/70532A61K38/00
    • Compositions and methods for costimulating T cells (i.e., increasing antigen-specific proliferation of T cells, enhancing cytokine production by T cells, stimulating differentiation ad effector functions of T cells and/or promoting T cell survival) are provided. Suitable compositions include variant B7-DC polypeptides, fragments and fusion proteins thereof. Variant B7-DC polypeptides have reduced binding affinity for the inhibitory PD-I ligand and substantially retain the ability to costiniulate T cells. Methods for using variant B7-DC polypeptides to stimulate immune responses in subjects in need thereof are provided.
    • 提供了共刺激T细胞的组合物和方法(即,增加T细胞的抗原特异性增殖,增强T细胞的细胞因子产生,刺激T细胞的分化和效应子功能和/或促进T细胞存活)。 合适的组合物包括变体B7-DC多肽,其片段和融合蛋白。 变体B7-DC多肽具有降低的对抑制性PD-1配体的结合亲和力,并且基本上保留了T细胞成本的能力。 提供了使用变体B7-DC多肽刺激有需要的受试者的免疫应答的方法。
    • 9. 发明申请
    • B7-H1 (CD274) ANTAGONISTS INDUCE APOPTOSIS OF TUMOR CELLS
    • B7-H1(CD274)拮抗剂诱导肿瘤细胞凋亡
    • WO2009089149A1
    • 2009-07-16
    • PCT/US2009/030104
    • 2009-01-05
    • THE JOHNS HOPKINS UNIVERSITYCHEN, Lieping
    • CHEN, Lieping
    • A61K39/395A61P35/00A61P37/04
    • C07K16/2827A61K2039/505
    • Compositions and methods for restoring killing of cancer cells are provided. Preferably, the compositions are administered to a subject in an effective amount to antagonize, inhibit, reduce, or block B7-H1 mediated signal transduction in cancer cells expressing B7-H1. It has been discovered that B7-H1 transmits an anti-apoptotic signal in cancer cells that increases the resistance of the cancer cells to CTL mediated cytolysis and to Fas induced cell death. It is believed that blocking the transmission of the anti- apoptotic signal by B7-H1 increases the susceptibility of the cancer cells to apoptosis and CTL cytolysis thereby enhancing the death of cancer cells. Preferred compounds or B7-H1 antagonists include antibodies that bind to B7-H1, B7-H1 receptors, or ligands of B7-H1 such as PD-I or B7-1. Additional B7-H1 antagonists include small molecules, for example small molecules that bind the cytoplasmic portion of B7-H1 or the extracellular portion of B7-H1 and inhibit, reduce, block or interfere with B7-H1 signal transduction. Methods for treating one or more symptoms associated with cancer or hyperproliferation are also provided.
    • 提供了恢复杀死癌细胞的组合物和方法。 优选地,组合物以有效量施用于受试者以拮抗,抑制,降低或阻断表达B7-H1的癌细胞中的B7-H1介导的信号转导。 已经发现B7-H1在癌细胞中传递抗细胞凋亡信号,其增加了癌细胞对CTL介导的细胞溶解和Fas诱导的细胞死亡的抗性。 相信通过B7-H1阻断抗凋亡信号的传递增加了癌细胞对凋亡和CTL细胞溶解的敏感性,从而增强了癌细胞的死亡。 优选的化合物或B7-H1拮抗剂包括结合B7-H1,B7-H1受体或B7-H1的配体如PD-1或B7-1的抗体。 另外的B7-H1拮抗剂包括小分子,例如结合B7-H1的细胞质部分或B7-H1细胞外部分并抑制,减少,阻断或干扰B7-H1信号转导的小分子。 还提供了治疗与癌症或过度增生相关的一种或多种症状的方法。