Development of a new methodology to induce immunological chimerism after allogeneic hematopoietic cell (HC) transplantation in a rhesus macaque model is described. The chimeric state was achieved using a non-myeloablative, helical tomotherapy-based total lymphoid irradiation (TomoTLI) conditioning regimen followed by donor HC infusions between 1-haplotype matched donor/recipient pairs. The technique was tested as a feasibility study in an experimental group of seven rhesus macaques that received the novel TomoTLI tolerance protocol and HC allo-transplants. Two tomotherapy protocols were compared: TomoTLI (n = 5) and TomoTLI/total-body irradiation (TBI) (n = 2). Five of seven animals developed mixed chimerism. Three of five animals given the TomoTLI protocol generated transient mixed chimerism with no graft-versus-host disease (GVHD) with survival of 33, 152 and >180 days. However, the inclusion of belatacept in addition to a single fraction of TBI resulted in total chimerism and fatal GVHD in both animals, indicating an unacceptable conditioning regimen.

描述了在恒河猴模型中异基因造血细胞 (HC) 移植后诱导免疫嵌合体的新方法的开发。嵌合状态是使用非清髓性、基于螺旋断层治疗的全淋巴照射 (TomoTLI) 预处理方案实现的，然后在 1 单倍型匹配的供体/受体对之间进行供体 HC 输注。该技术在接受新型 TomoTLI 耐受方案和 HC 同种异体移植的七只恒河猴实验组中作为可行性研究进行了测试。比较了两种断层放疗方案：TomoTLI (n = 5) 和 TomoTLI/全身照射 (TBI) (n = 2)。七只动物中有五只出现了混合嵌合现象。给予 TomoTLI 方案的五只动物中的三只产生了短暂的混合嵌合体，没有移植物抗宿主病 (GVHD)，存活时间分别为 33、152 和 >180 天。然而，除了单一部分的 TBI 外，包含 belatacept 会导致两种动物的完全嵌合和致命的 GVHD，这表明预处理方案是不可接受的。