2015-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/708584Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently still one, and sometimes the only one, curative treatment modality for various hematological diseases. Anyway, allogeneic immune response after allo-HSCT can result in graft-versus-host disease (GVHD), a major cause of failure and death after allo-HSCT, but also can mediate the graft-versus-tumor effects to eradicate primary disease. Adjustment of graft-versus-host immune response is therefore a dilemma after allo-HSCT, because over-suppression may increase the risk of disease relapse. On the other hand, cordycepin, also now known as 3-deoxyadenosine, is an adenosine analogue with various biological activities, including immune-modulatory and anti-leukemic effects. Our preliminary data showed that cordycepin can reduce the allogeneic immune reaction in vitro. With the reasonable hypothesis that cordycepin can effectively reduce the graft-versus-host immune response and attenuate GVHD after allo-HSCT, and our previously published findings that cordycepin can suppress the growth of leukemic cells via Wnt/β-catenin pathways, cordycepin will be an ideal compound to suppress or prevent GVHD without increased risk of relapse. Therefore, the following Specific Aims are planned in this Project to illustrate the immune-modulatory effects of cordycepin on GVHD: 1. To confirm the modulatory effects of cordycepin on allogeneic immune rejection in vitro, and then identify the key cytokines/signaling pathways involved in this process 2. To explore if cordycepin can be applied in treating GVHD after allo-HSCT in mice models 3. To explore if cordycepin can be applied in preventing GVHD after allo-HSCT in mice models 4. To identify the changes of cytokines and immune cell population while applying cordycepin in preventing or treating GVHD after allo-HSCT in mice models This Project, indeed, serve as a translational investigation to use cordycepin in preventing or treating GVHD after allo-HSCT for human. With the information from our preliminary data, it will be of great confidence that cordycepin can show preventive and therapeutic effects on GVHD after completing this Project. Along with our previous findings about the significant suppressive effects on human leukemia cells, cordycepin can serve as a better candidate to treat GVHD than other immune-suppressants, because it can reduce the risk of leukemia relapse with suppression of allogeneic immune response. Human clinical trials thereafter can be rapidly proceeded on the basis of the results from this Project, especially when we understand that cordycepin is an excellent candidate drug because it is a natural extract from old Chinese herb drugs and therefore the concern of safety is also minimal.cordycepin