Investigation of the functional characteristics of antibodies to therapeutic anti-human tumor necrosis factor alpha monoclonal antibody.
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.
Yucel
Aysegul
A
Department of Immunology, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.
Aral
Arzu L
AL
Basturk
Bilkay
B
Karakus
Resul
R
Aybay
Canan
C
Aybay
Cemalettin
C
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D007116:Immunization, Passive; D000069285:Infliximab; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab