Yucel Aysegul, Aral Arzu L, Basturk Bilkay, Karakus Resul, Aybay Canan, Aybay Cemalettin
Department of Immunology, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.
Immunol Lett. 2007 Aug 15;111(2):84-91. doi: 10.1016/j.imlet.2007.05.006. Epub 2007 Jun 21.
Humanized antibody-based treatment modalities represent an active area of investigation. Included in these strategies are passive administrations of monoclonal antibodies, which recognize tumor necrosis factor alpha (TNF-alpha). However, several problems associated with these types of treatment strategies have been reported in the literature. We attempted to address the issue related to unresponsiveness to infliximab that might be induced by anti-idiotype response to the passively administered humanized monoclonal antibody. The characteristics and functional importance of antibodies to infliximab (ATI) were investigated in human sera. We studied the binding characteristics of ATI to infliximab, TNF-alpha Receptor-I (RI, p55) and Receptor-II (RII, p75). In addition, cytotoxicity effect on L929 cells and blocking effects on the binding of TNF-alpha with infliximab and etanercept were also analyzed. On the basis of the results obtained from the experiments, it seems that the target epitope for ATI is related with somewhere else not residing in the region capable of generating "mirror image". The results presented indicate that ATI does not mimic the functional characteristics of TNF-alpha. However, ATI inhibited the binding properties of infliximab to TNF-alpha.
基于人源化抗体的治疗方式是一个活跃的研究领域。这些策略包括被动给予识别肿瘤坏死因子α（TNF-α）的单克隆抗体。然而，文献中已报道了与这类治疗策略相关的几个问题。我们试图解决因对被动给予的人源化单克隆抗体产生抗独特型反应而可能导致的对英夫利昔单抗无反应的问题。在人血清中研究了抗英夫利昔单抗抗体（ATI）的特性和功能重要性。我们研究了ATI与英夫利昔单抗、TNF-α受体-I（RI，p55）和受体-II（RII，p75）的结合特性。此外，还分析了其对L929细胞的细胞毒性作用以及对TNF-α与英夫利昔单抗和依那西普结合的阻断作用。根据实验结果，似乎ATI的靶表位与不在能够产生“镜像”的区域内的其他某个地方有关。呈现的结果表明ATI并不模拟TNF-α的功能特性。然而，ATI抑制了英夫利昔单抗与TNF-α的结合特性。
