Reed B R, Chen A B, Tanswell P, Prince W S, Wert R M, Glaesle-Schwarz L, Grossbard E B
Department of Medicinal and Analytical Chemistry, Genentech, Inc., South San Francisco 94080.
Thromb Haemost. 1990 Oct 22;64(2):276-80.
Sera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients' serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.
对1600多名在临床试验期间接受重组人组织型纤溶酶原激活剂（rt-PA）治疗的患者的血清进行了检测，以确定是否存在针对这种治疗药物的抗体。rt-PA通过多种给药方案用于几种不同的适应症。使用了两种不同形式的rt-PA；一种主要是双链形式，另一种主要是单链形式。采用灵敏的放射免疫沉淀试验检测患者治疗前后血清中针对rt-PA的抗体。在接受该检测的932名患者中，929名患者的t-PA抗体检测呈阴性。三名患者在治疗后出现低滴度抗体。在rt-PA治疗后2年内从这三名患者身上获取了额外的血清样本，其t-PA抗体检测呈阴性。由于阳性样本数量有限，未发现与rt-PA的剂量或类型、给药方案或临床诊断存在相关性。使用一种新型竞争性双位点酶联免疫吸附测定法在另外754名患者中证实了几乎没有抗体形成。可以得出结论，单次输注rt-PA几乎不会引发抗体形成，这表明在必要时可以进行重复治疗，而不会有链激酶或其衍生物所出现的免疫并发症风险。
