REDUCTION IN THE SEVERITY OF GRAFT-VERSUS-HOST DISEASE AND... : Transplantation (original) (raw)

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REDUCTION IN THE SEVERITY OF GRAFT-VERSUS-HOST DISEASE AND INCREASED SURVIVAL IN ALLOGENEIC MICE BY TREATMENT WITH MONOCLONAL ANTIBODIES TO CELL ADHESION ANTIGENS LFA-lα AND MALA-2

HARNING, RONALD1; PELLETIER, JOSEPHINE1; LUBBE, KLAUS2; TAKEI, FUMIO3; MERLUZZI, VINCENT J.1

Departments of Immunology and Molecular Biology, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877

1 Department of Immunology, Boehringer Ingelheim Pharmaceuticals, 90 East Ridge, Ridgefield, CT 06877.

2 Department of Molecular Biology, Boehringer Ingelheim Pharmaceuticals, 90 East Ridge, Ridgefield, CT 06877.

3 Department of Pathology, University of British Columbia, Vancouver, BC.

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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 BDFi mice as recipients, treatment of host mice with anti-LFA-lα (Ml7/ 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-lα and MALA-2 may provide a useful therapy for the treatment of GVHD.