Methods and Results.

Control (n= 5) and H2C12-treated (n= 7)(8–20 mg/kg iv on day− 1 followed by 10 mg/kg/day) adult male rhesus recipients were inoculated with GP120 protein antigen on day− 28 and− 1 and grafted with heterotopic abdominal hearts (day 0). Donor-recipient pairs were equally MLR mismatched (4329.8±1124.1 CPM controls vs. 7289.0±1926.5 treated, P= NS). Mean heart allograft survival as evaluated by daily abdominal palpation was significantly prolonged in high dose recipients (23.0±2.6, n= 4) vesus controls (8.2±1.3, n= 5, P< 0.02, Mann-Whitney U test). H2C12 treatment did not produce signs of cytokine release or toxicity, was nondepleting, but down-modulated PBL CD11a expression to 43.4±3.6%(n= 4) of control levels (n= 5) at day 7 as demonstrated by flow cytometry. It had no effect on postoperative Con A or MLR and did not prevent mAb clearance due to the rhesus-antihuman antibody response. The addition of mycophenolate mofitil prevented rhesus-antihuman antibody response with therapeutic H2C12 levels seen for> 35 days.

Conclusions.

The use of this mAb to block CD11a had the benefit of being a well tolerated, highly targeted therapy. These are the first results showing that monotherapy with anti-leukocyte function-associated antigen-1 mAb prolonged survival of MLR mismatched allogenic cardiac grafts in primates.