NOVEL TRANSFUSION BASED IMMUNE MODULATION

基于输血的新型免疫调节

• 批准号: 2839062
• 负责人: EDGAR G. ENGLEMAN
• 金额: $ 94.64万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-16 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839062
• 关键词: leukocyte transfusion; neoplasm /cancer immunology; transplantation immunology

Identification of functionally distinct leukocyte subpopulations combined with the recognition of the roles played by their surface proteins have created new opportunities for hematopoietic reconstitution and immune modulation, and provide the underlying rationale for this program project application. The proposed program brings together the collective expertise of investigators who have identified cell surface molecules that mediate immunomodulatory and alloimmune effects, developed techniques for isolating and activating rare types of mononuclear leukocytes, and demonstrated their therapeutic effects in model systems. The objective of our program is to utilize these discoveries to develop more effective immune cell based therapies, both autologous and allogeneic, for disorders ranging from malignancies to autoimmune disorders and graft-versus-host disease (GVHD). Four projects are described. Two of these projects seek to exploit the immunotherapeutic potential of dendritic cells pulsed with tumor derived antigens; one focuses on a treatment for malignant lymphoma a tumor of hematopoietic origin. while the other focuses on colorectal carcinoma a solid tumor. Two additional projects address novel approaches to the treatment and prevention of GVHD. One addresses the dual role of a polymorphic cell surface molecule, CD3 1, which appears to play an important pathogenetic role in GVHD; the other focuses on the ontogeny and mechanism of action of immunoregulatory CD3+,CD4-, CD8- T cell's derived from bone marrow. Supporting these projects are two cores, including an administrative and biostatistical core that will provide budgetary oversight, assistance in protocol design and statistical analysis and a flow cytometry core that will provide surface phenotype analysis and cell sorting capabilities. We believe that this interdisciplinary and highly interactive program will ultimately lead to the development of new and more potent forms of cell based immunotherapies for a variety of life-threatening disorders.

结合功能不同的白细胞亚群的鉴定 随着对其表面蛋白所发挥的作用的认识 为造血重建和免疫创造新的机会 调制，并提供该计划项目的基本原理 应用。拟议的计划汇集了集体 鉴定细胞表面分子的研究人员的专业知识 介导免疫调节和同种免疫作用，开发 分离和激活稀有类型单核细胞的技术 白细胞，并在模型系统中证明了它们的治疗效果。 我们计划的目标是利用这些发现来开发 更有效的基于免疫细胞的疗法，包括自体和 同种异体，适用于从恶性肿瘤到自身免疫性疾病的各种疾病 疾病和移植物抗宿主病（GVHD）。四个项目分别是 描述的。其中两个项目寻求利用免疫治疗 用肿瘤衍生抗原脉冲的树突状细胞的潜力；一 专注于治疗恶性淋巴瘤（一种造血系统肿瘤） 起源。而另一个则专注于结直肠癌（一种实体瘤）。 另外两个项目涉及新的治疗方法和 预防GVHD。解决多态性细胞的双重角色 表面分子 CD3 1，它似乎在重要的发病机制中发挥着重要作用 在 GVHD 中的作用；另一个侧重于个体发育和作用机制 源自骨髓的免疫调节性 CD3+、CD4-、CD8- T 细胞。 支持这些项目的是两个核心，包括行政和 生物统计核心将提供预算监督、援助 方案设计和统计分析以及流式细胞术核心 将提供表面表型分析和细胞分选功能。 我们相信这个跨学科且高度互动的项目 最终将导致新的、更有效的形式的开发 针对多种危及生命的疾病的细胞免疫疗法。