Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease.

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. The B10.D2-->Balb/c (H-2(d)) minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD, was used in this study. We demonstrated that a single injection of an agonistic monoclonal antibody (mAb) against CD137, a member of the tumor necrosis factor receptor superfamily, reverses skin fibrosis, ulceration, and alopecia, a dominant feature of cGVHD (cutaneous GVHD), 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 ameliorating cutaneous GVHD by anti-CD137 mAb. Taken together, these data indicate that the anti-CD137 mAb has a therapeutic effect on cutaneous GVHD by removing donor CD4(+) T cells that cause cutaneous GVHD. Thus, our study demonstrates an agonistic mAb, specific for a costimulatory molecule, as a possible target for therapeutic intervention in cutaneous GVHD.

• Authors: Juyang Kim, Hye J Kim, Keunhee Park, Jiyoung Kim, Hye-Jeong Choi, Hideo Yagita, Seok H Nam, Hong R Cho, Byungsuk Kwon
• Journal: Blood (Blood) Vol. 110 Issue 2 Pg. 776-82 (Jul 15 2007) ISSN: 0006-4971 [Print] United States
• PMID: 17363737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Bone Marrow Transplantation (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Graft vs Host Disease (immunology, therapy)
• Immunotherapy
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Mice, Inbred Strains
• Stem Cell Transplantation (adverse effects)
• Transplantation, Homologous