LACK OF IN-VITRO SYNERGY OF CLINICALLY USED ANTIBODIES SPECIFIC FOR ICAM-1 AND LFA-1

Antibodies blocking adhesion molecules such as leucocyte function anti gen (LEA)-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 s ingle application of antibodies against LFA-1 and ICAM-1 can induce to lerance 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 BIR R1 (alpha-ICAM-1) on human cells in vitro alone and in combination. Al logeneic venous endothelial cells, the lymphoblastoid cell line MSAB o r peripheral blood mononuclear cells were used as stimulators. DNA syn thesis, IL-2 production and cytotoxic T cell lysis were measured to as sess T cell response. The strongest antibody effects were seen when en dothelial cells were used as stimulators with the T cell response bein g assessed by IL-2 production. Most assays showed a similar immunosupp ressive effect of LFA-1 and ICAM-1 blocking while the combination of b oth antibodies was not significantly more effective than each antibody alone. Thus our data do not provide a rationale for clinical trials u sing a combination of these antibodies.