HUMANIZED ANTIGP39 AB FOR AUTOIMMUNITY/GRAFT REJECTION

用于自身免疫/移植排斥的人源化 ANTIGP39 AB

• 批准号: 2672688
• 负责人: PETER BRAMS
• 金额: $ 34.85万
• 依托单位: IDEC PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672688
• 关键词: CD40 molecule; CHO cells; Callithricidae; Macaca fascicularis; SCID mouse; antibody specificity; disease /disorder model; experimental allergic encephalomyelitis; glycoproteins; hybrid antibody; immunosuppressive antileukocyte serum; method development; monoclonal antibody; pharmacokinetics; protein purification; species difference; transfection

An antibody specific for human gp39 is being developed to use in the treatment of autoimmune diseases, such as systemic lupus erythematosis, idiopathic thrombocytopenia purpura, multiple sclerosis and rheumatoid arthritis. In addition, the anti-gp39 antibody may have significant therapeutic value in preventing rejection of transplanted tissues and organs. The interaction of gp39 with its receptor, CD40, has been shown to play a critical role in the regulation of humoral and cell-mediated immunity. Functional studies have demonstrated that the treatment of mice with anti- gp39 antibodies that block gp39-CD40 interaction inhibits antibody and cell-mediated immune responses against thymus dependent antigens. Compelling evidence in animal models indicates that anti-gp39 administration prevents a variety of autoimmune processes, including autoantibody production, and interferes with allograft rejection. A humanized anti-human gp39 antibody that blocks gp30-CD40 interaction has been generated. We propose to continue its in vitro and in vivo characterization and to develop a Chinese hamster ovary cell line transfectant capable of producing very high levels of the antibody. The characterization of the anti-gp39 antibody will be extended to preclinical models of autoimmune disease and allograft rejection in non-human primates. PROPOSED COMMERCIAL APPLICATION: The goal of this project is to develop a humanized antibody specific for human gp39 for use in the treatment of autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, diabetes, and idiopathic thrombocytopenic purpura, and of graft-versus-host-disease and graft rejection.

正在开发一种对人gp 39特异性的抗体， 治疗自身免疫性疾病，如系统性狼疮性肾炎， 特发性血小板减少性紫癜、多发性硬化和类风湿 关节炎 此外，抗gp 39抗体可具有显著的免疫抑制作用。 预防移植组织排斥反应的治疗价值， 机关 gp 39与其受体CD 40的相互作用已被证明在免疫调节中起作用。 在体液和细胞介导的免疫调节中起关键作用。 功能研究表明，用抗- 阻断gp 39-CD 40相互作用的gp 39抗体抑制抗体和 针对胸腺依赖性抗原的细胞介导的免疫应答。 动物模型中令人信服的证据表明，抗gp 39 给药可预防多种自身免疫过程，包括 自身抗体的产生，并干扰同种异体移植排斥。 一种阻断gp 30-CD 40相互作用的人源化抗人gp 39抗体， 被生成。 我们建议继续其在体外和体内 鉴定和开发中国仓鼠卵巢细胞系 能够产生非常高水平的抗体的转染子。 的 抗gp 39抗体的表征将扩展到临床前 非人类自身免疫性疾病和同种异体移植排斥模型 灵长类动物 建议的商业应用：该项目的目标是开发 一种特异于人gp 39的人源化抗体，其用于治疗 自身免疫性疾病，如系统性红斑狼疮、类风湿性 关节炎、多发性硬化症、重症肌无力、糖尿病和特发性 血小板减少性紫癜，移植物抗宿主病和移植物 排斥反应