COMPOSITIONS AND METHODS FOR SUPPRESSION OF INHIBITOR FORMATION AGAINST COAGULATION FACTORS IN HEMOPHILIA PATIENTS
    67.
    发明申请
    COMPOSITIONS AND METHODS FOR SUPPRESSION OF INHIBITOR FORMATION AGAINST COAGULATION FACTORS IN HEMOPHILIA PATIENTS 有权
    用于抑制抑制剂形成的组合物和方法,以防止HEMOPHILA患者的凝血因子

    公开(公告)号:US20160289277A1

    公开(公告)日:2016-10-06

    申请号:US15037045

    申请日:2014-11-17

    摘要: Protein replacement therapy for patients with hemophilia or other inherited protein deficiencies is often complicated by pathogenic antibody responses, including antibodies that neutralize the therapeutic protein or that predispose to potentially life-threatening anaphylactic reactions by formation of IgE. Using murine and canine hemophilia as a model, we have developed a prophylactic protocol against such responses that is non-invasive and does not include immune suppression or genetic manipulation of the patient's cells. Oral delivery of a coagulation factor expressed in chloroplasts, bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies in protein replacement therapy. Inhibitor titers were mostly undetectable and up to 100-fold lower in treated subjects when compared to controls. Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous coagulation factor protein. Finally, the method can effectively be used to reverse or reduce undesirable pre-existing inhibitor titers.

    摘要翻译: 对于患有血友病或其他遗传性蛋白质缺乏症的患者,蛋白质替代疗法通常由致病性抗体反应复杂化,包括中和治疗性蛋白质的抗体或易于形成IgE的潜在的威胁生命的过敏反应的抗体。 使用鼠和犬血友病作为模型,我们已经制定了一种针对这种非侵入性反应的预防方案,不包括对患者细胞的免疫抑制或遗传操作。 在植物细胞中生物封装的叶绿体中表达的凝血因子的口服递送在蛋白质替代疗法中有效阻断了抑制性抗体的形成。 与对照相比,抑制剂滴度几乎不可检测,并且在治疗的受试者中高达100倍。 此外,该治疗消除了在静脉内凝血因子蛋白质暴露四至六次后发生的致命过敏反应。 最后,该方法可有效地用于逆转或减少不期望的预先存在的抑制剂滴度。