GRAFT-VERSUS-HOST DISEASE IN ALLOGENEIC BONE MARROW TRANSPLANTATION

异体骨髓移植中的移植物抗宿主病

• 批准号: 3916416
• 负责人: R E GRESS
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916416
• 关键词: T lymphocyte; antibody specificity; blood banks; bone marrow preservation; bone marrow transplantation; combination cancer therapy; complement; cryopreservation; graft versus host disease; histocompatibility antigens; homologous transplantation; human subject; human tissue; immunosuppression; leukocyte activation /transformation; monoclonal antibody; tissue donors

Graft-versus-host disease (GvHD) is dependent in its generation on the presence of immune competent T cells in the donor marrow with specificity for allogeneic antigens of the host. The activation of these cells in the host after infusion and the resultant tissue injury is clinically recognized as GvHD. One approach to preventing GvHD is the removal of these T cells from the marrow inoculum. We have pursued T cell depletion of human marrow for the purpose of preventing GvHD in marrow transplantation across MHC differences in man by the use of monoclonal antibodies specific for cell surface molecules unique to T cells in combination with complement. Two such antibodies have been derived, one with specificity for CD2 (sheep red blood cell receptor) and one which defines a novel T cell determinant. The latter antibody precipi- tates a 92 KD molecule and a predominant 45 KD band under non- reducing conditions and reducing conditions, respectively. These two antibodies, in combination with CD7 and CD5 specific antibodies, have been used to carry out studies in human bone marrow T cell depletion. To quantitate T cells remaining in marrow after such depletions, a limiting dilution assay was developed which detects T cells at a level of one T cell per 10-10 marrow cells. A bank of cryopreserved marrows depleted of T cells by a combination of monoclonal antibodies and complement, with the extent of that depletion assessed by limiting dilution assay, has been established and a clinical protocol developed to assess the feasibility of utilizing these marrows in the treatment of aggressive malignancy with marrow ablative combination chemotherapy and radiotherapy.

移植物抗宿主病（GvHD）的产生依赖于 供体骨髓中存在免疫活性T细胞， 对宿主同种异体抗原的特异性。 激活 这些细胞在输注后在宿主体内的数量以及由此产生的组织 损伤在临床上被认为是GvHD。 的一种方法 防止GvHD的方法是从骨髓中清除这些T细胞 接种物。 我们已经追踪了人类骨髓的T细胞耗竭， 跨MHC骨髓移植预防GvHD的目的 使用针对以下疾病的单克隆抗体在人类中产生的差异 T细胞特有的细胞表面分子与 补体 已经衍生出两种这样的抗体，一种具有 对CD2（绵羊红细胞受体）的特异性， 定义了一种新型T细胞决定簇。 后一种抗体沉淀- 在非变性条件下显示92 KD分子和主要的45 KD条带， 还原条件和还原条件。 这些 两种抗体，与CD7和CD5特异性 抗体，已被用于在人骨中进行研究 骨髓T细胞耗竭。 定量骨髓中残留的T细胞 经过这样的消耗后，开发了有限稀释测定法 它检测T细胞的水平是每10 - 10个骨髓中有一个T细胞 细胞 一个冷冻保存的骨髓库， 单克隆抗体和补体的组合， 通过有限稀释试验评估的消耗程度， 制定了临床方案，以评估 利用这些骨髓治疗 侵袭性恶性肿瘤骨髓清除联合化疗 和放射治疗。