Reduction in the severity of graft-versus-host disease and increased survival in allogenic mice by treatment with monoclonal antibodies to cell adhesion antigens LFA-1 alpha and MALA-2.
Bone marrow transplantation is a therapeutic treatment for many life-threatening hematologic disorders, especially leukemia and certain immune deficiency diseases. However, acute graft-versus-host disease is often associated with bone marrow transplantation. In mice, allogeneic GVHD appears to be mediated by both host natural killer cells and donor T cells. In vitro and in vivo experiments demonstrate that treatment with either YN1/1.7 or M17/4.2 mabs is immunomodulatory and inhibits both the mixed lymphocyte reaction and natural killer cell activity. In addition, utilizing an allogeneic model of acute, lethal GVHD with C57B1/6 mice as donors and sublethally irradiated BDF1 mice as recipients, treatment of host mice with anti-LFA-1 alpha (M17/4.2) or anti-MALA-2 (YN1/1.7) mabs at a dose of 10 mg/kg/day for 10 days significantly reduced GVHD and enhanced survival. Mabs to lymphocyte adhesion molecules such as LFA-1 alpha and MALA-2 may provide a useful therapy for the treatment of GVHD.
Harning
R
R
Department of Immunology, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877.
Pelletier
J
J
Lubbe
K
K
Takei
F
F
Merluzzi
V J
VJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D007694:Killer Cells, Natural / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D004338:Drug Combinations; D016169:Lymphocyte Function-Associated Antigen-1; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7