Costimulatory molecule-targeted immunotherapy of chronic graft-versus-host disease (88.17)

Abstract Chronic graft-versus-host disease (cGVHD) is an increasingly frequent complication of allogeneic stem cell transplantation. Current therapies for cGVHD reduce symptoms but are not cures. Using the B10.D2„³Balb/c (H-2d) minor histocompatibility antigen-mismatched model which reflects clinical and pathological symptoms of human cGVHD, we show that a single injection of an agonistic monoclonal antibody (mAb) to CD137, a member of tumor necrosis factor receptor superfamily, reverses skin fibrosis, ulceration and alopecia, ultimately improving general health conditions. The reversal is associated with markedly reduced CD4+ T cell cytokines and increased apoptosis of donor CD4+ T cells. The Fas pathway is required for the therapeutic effect of anti-CD137 mAb on cGVHD. Taken together, these data indicate that anti-CD137 mAb has a therapeutic effect on cGVHD by removing donor CD4+ T cells mediating cGVHD. Our study demonstrates an agonistic mAb specific for a costimulatory molecule as a possible target for therapeutic intervention in cGVHD.