Inhibition of dog platelet function by in vivo infusion of F(ab')2 fragments of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor.
Inhibition of dog platelet function by in vivo infusion of F(ab')2 fragments of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor.
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DOI：
10.1182/blood.v66.6.1456.bloodjournal6661456
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发表时间：
1985-12
期刊：
影响因子：
20.3
通讯作者：
B. Coller;L. Scudder
中科院分区：
文献类型：
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作者：
B. Coller;L. Scudder
为了评估体外抑制血小板功能的单克隆抗体作为体内治疗剂的潜力，将鼠单克隆抗体（7 E3）的F（ab ′）2片段（0.17至0.81 mg/kg）输注到三只狗中，所述鼠单克隆抗体（7 E3）结合血小板糖蛋白IIb和/或IIIa并阻断ADP诱导的血小板聚集。输注后不久，从犬中回收的血小板显示出对腺苷二磷酸的聚集反应降低，最高剂量几乎产生完全抑制。这些血小板还显示出结合125 I-7 E3的能力降低，这被认为反映了未标记的F（ab '）2片段对位点的占据。在最高剂量下，结合降低85%，反映了每个血小板约44，000个7 E3 F（ab '）2分子的结合。抗体输注后血小板计数下降小于20%，并且没有犬显示自发性出血。聚集和结合结果均在一天内恢复正常。我们的结论是，有可能通过体内输注抗血小板单克隆抗体的F（ab '）2片段来深刻抑制血小板功能，而不产生自发性出血或显著的血小板减少症。
To assess the potential of monoclonal antibodies that inhibit platelet function in vitro as in vivo therapeutic agents, F(ab')2 fragments (0.17 to 0.81 mg/kg) of a murine monoclonal antibody (7E3) that binds to platelet glycoproteins IIb and/or IIIa and blocks platelet aggregation induced by ADP were infused into three dogs. Soon after infusion, platelets recovered from the dogs showed a decreased aggregation response to adenosine diphosphate, with the highest dose producing nearly total inhibition. These platelets also showed decreased ability to bind 125I-7E3, which was assumed to reflect occupancy of the sites by the unlabeled F(ab')2 fragments. At the highest dose, the binding decreased by 85%, reflecting the binding of approximately 44,000 molecules of 7E3 F(ab')2 per platelet. Platelet counts decreased after antibody infusion by less than 20%, and none of the dogs showed spontaneous bleeding. Both the aggregation and binding results reverted toward normal within one day. We conclude that it is possible to profoundly inhibit platelet function by in vivo infusion of F(ab')2 fragments of a monoclonal antiplatelet antibody without producing spontaneous hemorrhage or significant thrombocytopenia.