EFFICACY OF CD28 ANTIBODY FOR GVHD PREVENTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 先前的研究表明，施用激动性CD 28抗体可以预防小鼠中的GVHD。在迄今为止的研究中，我们发现在狒狒中，在MHC半相合HCT后，施用CD 28抗体本身不足以预防严重的急性GVHD。随后的研究因难以获得合适的供体-受体配对而推迟。另外两只狒狒已经用CD 28抗体与甲氨蝶呤和他克莫司联合治疗。两名受者均迅速自体造血恢复，无GVHD。自体造血恢复最有可能通过与全身照射（TBI）期间意外单向暴露于直线加速器相关的脊柱和骨盆骨的亚清髓性照射来解释。

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).