PHARMACODYNAMICS OF PROPHYLACTIC ANTIREJECTION THERAPY WITH AN ANTI-INTERLEUKIN-2 RECEPTOR MONOCLONAL-ANTIBODY (BT563) AFTER HEART AND KIDNEY-TRANSPLANTATION

A mouse monoclonal antibody (BT563) directed to the cu-chain of the IL -2 receptor was administrated immediately after transplantation in a d ose of 10 mg/day prophylactically to 30 heart transplant recipients (H Tx) and 40 renal transplant recipients (RTx) to induce immunosuppressi on. Plasma levels increased to a plateau level of 5300 ng/ml in RTx an d 5900 ng/ml in RTx. BT563 plasma disappearance curves gives a mean T- 1/2 of respectively 39 h (range 14-112 h) and 42 h (range 8-122 h) for HTx and RTx respectively. The CD25 marker (IL-2R) on the peripheral b lood lymphocytes disappeared within hours after the first gift and ret urned to normal within 0-20 days after the last gift. In HTx more ofte n CD25(+) cells were found in the presence of BT563 and more rejection s occurred shortly after discontinuation of BT563 compared to the RTx group. Rejectors and non-rejectors within the HTX group did not differ with respect to the period of depletion of CD25 positive cells in the peripheral blood. In 56% of the patients a substantial IgM antibody r esponse was detected. This response was similar for HTx and RTx and no t related to rejection. The frequency of IgG responses was low in both HTx (13%) and RTx (21%) patients and the IgG response was not related with graft rejection or with antirejection treatment. Peripheral moni toring showed that mAb plasma levels, antimurine antibody responses an d number of CD25 positive cells were not related with the clinical res ults. The mAb BT563 proved to be safe with respect to the generation o f antimurine antibodies and, when given in combination with CsA, is a therapy with a potential for high efficacy.