We are developing an MHC-haploidentical allogeneic bone marrow transplantation model that parallels human treatment and can be used to decipher the immunologic impact of post-transplantation cyclophosphamide (PTCy). We are studying the impact of this therapy on clinical endpoints (survival, graft-versus-host disease, weight); accompanying these studies is a detailed characterization of the immunologic and histopathologic changes associated with this approach. Once the mechanisms by which PTCy prevents GVHD uncovered, we will use this understanding as a basis to explore how to refine this BMT approach clinically towards the clinical goals of further reducing graft-versus-host disease, ensuring reliable engraftment with minimal conditioning, and serving as a platform for other therapies to reduce relapse. We also are exploring the impact of PTCy on human T cells in mixed lymphocyte cultures with the goal of improving our understanding of the immunologic impact of PTCy in order to improve clinical outcomes. Lastly, we have begun a study to investigate if antigen-specific cellular therapy can be safely and effectively integrated with haplo BMT using PTCy.
