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 alpha-chain of the IL-2 receptor was administrated immediately after transplantation in a dose of 10 mg/day prophylactically to 30 heart transplant recipients (HTx) and 40 renal transplant recipients (RTx) to induce immunosuppression. Plasma levels increased to a plateau level of 5300 ng/ml in HTx and 5900 ng/ml in RTx. BT563 plasma disappearance curves gives a mean T1/2 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 blood lymphocytes disappeared within hours after the first gift and returned to normal within 0-20 days after the last gift. In HTx more often CD25+ cells were found in the presence of BT563 and more rejections 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 response was detected. This response was similar for HTx and RTx and not 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 monitoring showed that mAb plasma levels, antimurine antibody responses and number of CD25 positive cells were not related with the clinical results. The mAb BT563 proved to be safe with respect to the generation of antimurine antibodies and, when given in combination with CsA, is a therapy with a potential for high efficacy.
Hesse
C J
CJ
Department of Internal Medicine, Erasmus University Rotterdam, University Hospital Rotterdam, Dijkzigt, The Netherlands.
van Gelder
T
T
Vaessen
L M
LM
Knoop
C J
CJ
Balk
A H
AH
Yzermans
J N
JN
Jutte
N H
NH
Weimar
W
W
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D015375:Receptors, Interleukin-2