Friday, April 4, 2025
4/4/2025
Cell therapy for GvHD - Abstract. Hematologic malignancies are often treated with allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT is complicated by graft-vs-host disease (GvHD), a severe, potentially lethal complication initiated when donor alloreactive T cells attack host cells and organs. Despite the administration of prophylactic regimens for aGVHD as standard pre-transplantation therapy, up to 60% of these patients develop aGVHD of grade II or higher, and require additional immunosuppressive intervention. Thus, there is an urgent need to improve pre-transplantation therapies to prevent aGVHD. We identified a probiotic exopolysaccharide (EPS) that induces tolerogenic dendritic cells (DCs) that inhibit T cell proliferation, and we found that EPS-treated human DCs (EPS-DCs) both inhibited T cell proliferation in mixed lymphocyte reactions, and significantly increased survival of humanized NSG-HLA-A2 mice after transplantation with human peripheral blood mononuclear cells (hPBMC). The data indicate that a cell-based therapy using EPS-DCs can mitigate aGvHD, and the goal of this grant is to optimize the EPS-DC dosage for maximum protection from GvHD, and to determine the molecular mechanism by which these EPS-DCs inhibit proliferation of alloreactive T cells both in vitro and in vivo. These studies will provide a novel cell-based therapy for preventing GvHD in patients receiving HSCT. This cell therapy will be translatable to humans because large numbers of EPS-DCs can be generated and frozen in bulk and used as “off the shelf” treatment, for all patients, independent of MHC types.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).