ANTICD154 THERAPY & ALLOGENEIC BONE MARROW TRANSPLANTS

ANTICD154治疗

• 批准号: 2717421
• 负责人: RANDOLPH J. NOELLE
• 金额: $ 10万
• 依托单位: IDEC PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2717421
• 关键词: CD antigens; CD40 molecule; SCID mouse; bone marrow transplantation; drug design /synthesis /production; graft versus host disease; hematopoietic stem cells; human tissue; immunological substance; immunosuppressive; immunotherapy; ligands; monoclonal antibody

DESCRIPTION: (Adapted from the applicant's abstract) CD40 and its ligand, CD154, have been shown to play an integral role in the regulation of cell- mediated immunity. As a result of interfering with antigen presenting cell function and diminishing inflammatory responses, anti-CD154 can ablate the immune response to transplantation antigens; thus opening the way for the transplantation of allogeneic/xenogeneic tissues and organs. A humanized anti-human CD154 has been produced and the purpose of this proposal is to evaluate the potential value of this antibody as an immunosuppressive agent for allogeneic bone marrow transplantation [ABMT]. There are a number of critical feasibility studies that are needed that will help resolve if this antibody has potential usefulness in blocking graft vs host disease [GVHD] and facilitating the engraftment of human hematopoetic stem cells in humans. To evaluate its potential utility in managing GVHD in humans, the first goal will be to determine if h-anti-hCD154 blocks human T cell responses to xenoantigens in vivo [hu-SCID model]. The second goal is to determine if human anti-hCD154 interferes with the engraftment of human hematopoetic stem cells in vivo. The last goal is to determine if h-anti-hCD154 blocks graft vs leukemia [GVL] responses, a response that significantly contributes to the eradication of residual tumor cells and long lasting remission. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述：(改编自申请人的摘要)CD40及其配体， CD154，已被证明在调节细胞- 中介免疫。作为干扰抗原提呈的结果 细胞功能和减少炎症反应，抗CD154可以 消除对移植抗原的免疫反应；从而打开 异体/异种组织和器官移植的途径。 人源化的抗人CD154已经被生产出来，其目的是 建议评估这种抗体作为一种 异基因骨髓移植的免疫抑制剂[ABMT] 有许多关键的可行性研究是必要的， 将有助于解决该抗体是否具有潜在的阻断作用 移植物抗宿主病[GVHD]和促进人类移植 人类的造血干细胞。 为了评估它在管理人类GVHD方面的潜在效用，第一个 目标将是确定h-抗hCD154是否阻止人类T细胞反应 体内对异种抗原的敏感性[HU-SCID模型]。第二个目标是确定 人抗hCD154抗体是否干扰人造血细胞的植入 体内的干细胞。最后一个目标是确定h-anti-hCD154是否阻断 移植物与白血病[GVL]反应，这一反应显著 有助于消除残留的肿瘤细胞并持久 减刑。 建议的商业应用：不可用