Lack of in vitro synergy of clinically used antibodies specific for ICAM-1 and LFA-1.
Antibodies blocking adhesion molecules such as leucocyte function antigen (LFA)-1 (CD11a) and intercellular adhesion molecule (ICAM)-1 (CD54) are currently under clinical investigation for rejection prophylaxis in organ transplantation. In a murine model a combined though not a single application of antibodies against LFA-1 and ICAM-1 can induce tolerance towards heart transplants. No information regarding a possible synergistic action in man is as yet available. To fill this blank we tested the immunosuppressive capacity of ANTILFA (alpha-LFA-1)- and BIRR1 (alpha-ICAM-1) on human cells in vitro alone and in combination. Allogeneic venous endothelial cells, the lymphoblastoid cell line MSAB or peripheral blood mononuclear cells were used as stimulation. DNA synthesis, IL-2 production and cytotoxic T cell lysis were measured to assess T cell response. The strongest antibody effects were seen when endothelial cells were used as stimulators with the T cell response being assessed by IL-2 production. Most assays showed a similar immunosuppressive effect of LFA-1 and ICAM-1 blocking while the combination of both antibodies was not significantly more effective than each antibody alone. Thus our data do not provide a rationale for clinical trials using a combination of these antibodies.
Römer
K
K
Institute of Immunology, University of Kiel, Germany.
Herwartz
C
C
Steinhoff
G
G
Steinmann
J
J
D019138:Antibodies, Blocking / Q000008:administration & dosage* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D000918:Antibody Specificity; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000378:metabolism; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007376:Interleukin-2 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D016377:Organ Transplantation / Q000379:methods
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1