Donor-spEcific monocyte-derived suppressor CEll therapy in traNsplantaTion – DECENT

Donor-specific tolerance has long been the crowning achievement in transplantation, with the ultimate goal to avoid the complications of long-term immunosuppression such as cancer. In patients, immune tolerance, defined as a state wherein donor and recipient immune cells coexist, has been successfully observed through mixed chimerism after combined kidney and bone marrow transplantation. However, this type of combined transplantation requires conditioning regimens and donor lymphocyte infusion that could lead to severe complications, such as disastrous graft-versus-host disease (GVHD). Thus, suggesting new tolerogeneic strategies is essential. Human monocyte-derived suppressor cells (hereinafter referred as HuMoSC) are competent immunosuppressive cells derived from monocytes. They were showed to inhibit effector T cell proliferation but also to induce FOXP3-expressing regulatory T cell population (Treg) in vitro as well as to significantly mitigate GvHD in vivo. However, HuMoSC cellular therapy in transplantation faces several challenges including the vast numbers of peripheral blood mononuclear cells (PBMC) needed to generate HuMoSC as well as the ratio of HuMoSC required to outcompete alloreactive PBMC (1:1). Here we propose to tackle these challenges with an edge-cutting new immunosuppressive HuMoSC-based cell-therapy strategy built on gene engineering and endowed with high translational potential.