Exploiting Fas-mediated autocrine apoptosis of donor alloreactive T cells as an effective approach to prevent acute graft-versus-host disease in a humanized mouse model

Abstract Acute GVHD initiated by donor T cells is a barrier to allogeneic bone marrow transplantation. Pan cell elimination from the graft associated with failure of stem engraftment and delayed immune reconstitution. upregulate Fas receptor on their surface following activation become susceptible FasL-mediated apoptosis. The objective this study was target Fas-mediated apoptosis for preferential alloreactive cells. We previously reported novel form FasL protein chimeric streptavidin (SA-FasL). Mouse human lymphocytes were modified biotin, followed engineering SA-FasL taking advantage biotin's high affinity SA. SA-FasL-engineered assessed autocrine in vitro vivo. NSG mice transplanted 10 7human PBMC used as an acute xenogeneic model. induced Mice had significantly lower numbers spleen liver analyzed five days post-transplantation compared recipients SA-engineered Recipients developed median survival time 15 days. In marked contrast, sixty percent PBMCs survived 60-day observation period showed minimal clinical scores. Transient display provides practical clinically applicable effective approach prevent significant translational potential.