EFFICACY OF CD28 ANTIBODY FOR GVHD PREVENTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 先前的研究表明，注射激动型CD28抗体可以预防小鼠的GVHD。在到目前为止的研究中，我们发现CD28抗体本身并不足以预防MHC半相合红细胞移植后的严重急性移植物抗宿主病。随后的研究因难以获得合适的供受者对而被推迟。另外两只狒狒已经接受了CD28抗体与甲氨蝶呤和他克莫司的联合治疗。两位受者均在无移植物抗宿主病的情况下迅速自体造血恢复。自体造血恢复最有可能是由于全身照射(TBI)期间无意中单向暴露于直线加速器而导致的脊柱和骨盆骨亚清髓性照射所致。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies showed that administration of an agonistic CD28 antibody could prevent GVHD in mice. In studies to date, we found that administration of a CD28 antibody was not sufficient by itself to prevent severe acute GVHD after MHC-haploidentical HCT in a baboon. Subsequent studies were delayed by difficulty in obtaining appropriate donor-recipient pairs. Two additional baboons have been treated with the CD28 antibody in combination with methotrexate and tacrolimus. Both recipients had prompt autologous hematopoietic recovery without GVHD. Autologous hematopoietic recovery was most likely explained by sub-myeloablative irradiation of the spine and pelvic bones related to inadvertent unidirectional exposure to the linear accelerator during total body irradiation (TBI).