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.