Isaacs J D
Department of Pathology, University of Cambridge, UK.
Semin Immunol. 1990 Nov;2(6):449-56.
The antiglobulin response to administered therapeutic monoclonal antibodies is currently one of the major limitations of antibody therapy. In the presence of a normally functioning immune system a response is inevitable after 1-2 weeks of treatment with most agents. The anti-idiotype arm of the response will inhibit the binding of antibody to target antigen, whilst both this and the anti-isotype component act to accelerate antibody clearance. Although the antiglobulin response appears to follow the rules governing immunity to soluble protein antigens the idiotypic epitopes of cell-binding antibodies seem to be particularly immunogenic. The consequence of this has been the failure to induce tolerance to therapeutic antibodies by conventional approaches and, in turn this has provided much of the stimulus to the technology of antibody 'humanisation'. It is still uncertain, however, if even a humanised antibody will remain invisible to the immune system.
目前，对所给予的治疗性单克隆抗体的抗球蛋白反应是抗体治疗的主要限制之一。在免疫系统功能正常的情况下，使用大多数药物治疗1 - 2周后，反应是不可避免的。反应中的抗独特型臂会抑制抗体与靶抗原的结合，而这一成分和抗同种型成分都会加速抗体清除。尽管抗球蛋白反应似乎遵循针对可溶性蛋白质抗原的免疫规则，但细胞结合抗体的独特型表位似乎具有特别强的免疫原性。其结果是，传统方法未能诱导对治疗性抗体的耐受性，进而这也为抗体“人源化”技术提供了很大的推动力。然而，即使是人源化抗体是否仍能对免疫系统保持隐匿性，目前仍不确定。
