Hesse C J, van Gelder T, Vaessen L M, Knoop C J, Balk A H, Yzermans J N, Jutte N H, Weimar W
Department of Internal Medicine, Erasmus University Rotterdam, University Hospital Rotterdam, Dijkzigt, The Netherlands.
Immunopharmacology. 1995 Sep;30(3):237-46. doi: 10.1016/0162-3109(95)00028-r.
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.
一种针对白细胞介素-2受体α链的小鼠单克隆抗体（BT563），在移植后立即以10毫克/天的剂量预防性给予30名心脏移植受者（HTx）和40名肾移植受者（RTx），以诱导免疫抑制。HTx患者的血浆水平升至5300纳克/毫升的平台期水平，RTx患者则升至5900纳克/毫升。BT563的血浆消除曲线显示，HTx和RTx的平均半衰期分别为39小时（范围14 - 112小时）和42小时（范围8 - 122小时）。首次给药后数小时内，外周血淋巴细胞上的CD25标记物（IL - 2R）消失，并在最后一次给药后0 - 20天内恢复正常。与RTx组相比，在BT563存在的情况下，HTx中更常发现CD25 +细胞，且在停用BT563后不久发生更多排斥反应。HTX组中的排斥者和非排斥者在外周血中CD25阳性细胞的耗竭期方面没有差异。56%的患者检测到显著的IgM抗体反应。HTx和RTx的这种反应相似，且与排斥反应无关。HTx（13%）和RTx（21%）患者中IgG反应的频率都很低，且IgG反应与移植物排斥或抗排斥治疗无关。外周监测显示，单克隆抗体血浆水平、抗鼠抗体反应和CD25阳性细胞数量与临床结果无关。就抗鼠抗体的产生而言，单克隆抗体BT563被证明是安全的，并且与环孢素A联合使用时，是一种具有高效潜力的疗法。
