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: 3813468
• 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/3813468
• 关键词: CD antigens; CD8 molecule; T lymphocyte; antibody formation; antibody specificity; blood banks; bone marrow preservation; bone marrow transplantation; combination cancer therapy; complement; cryopreservation; graft versus host disease; histocompatibility antigens; homologous transplantation; human tissue; immunosuppression; leukocyte activation /transformation; monoclonal antibody; neoplasm /cancer immunotherapy; surface antigens; 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 precipitates 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(5)-10(6) 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. The techniques developed for the removal of normal T cells from allogeneic marrow have also been applied to the removal of malignant T cells from autologous marrow. A clinical protocol has been developed to assess the feasibility of utilizing these marrows in the treatment of aggressive T cell malignancies with marrow ablative chemotherapy and radiotherapy.

移植物抗宿主病（GVHD）的产生依赖于