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

Transplantation. 1991 Nov;52(5):842-5. doi: 10.1097/00007890-199111000-00017.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Cytotoxicity Tests, Immunologic
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Graft Survival
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Killer Cells, Natural / drug effects
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Drug Combinations
  • Lymphocyte Function-Associated Antigen-1
  • Tumor Necrosis Factor Receptor Superfamily, Member 7