Biased anti-idiotype response in rabbits leads to high-affinity monoclonal antibodies to biologics
| Autor: | Lisanne Dijk, Astrid van Leeuwen, Theo Rispens, Jorn Jeremiasse, Dorien Kos, Floris C. Loeff, Christina Großerichter-Wagener |
|---|---|
| Přispěvatelé: | Landsteiner Laboratory, AII - Inflammatory diseases |
| Rok vydání: | 2020 |
| Předmět: |
Idiotype
medicine.drug_class Immunology Biology Monoclonal antibody Antibodies Monoclonal Humanized 03 medical and health sciences Immunoglobulin Fab Fragments 0302 clinical medicine Reslizumab Report medicine Immunology and Allergy Animals Humans 030304 developmental biology 0303 health sciences Antibodies Monoclonal Dupilumab Antibodies Anti-Idiotypic anti-idiotype antibodies 030220 oncology & carcinogenesis Monoclonal Antibody Formation biology.protein PK/ADA assays Secukinumab Immunization Rabbits Antibody Mepolizumab rabbit monoclonal antibodies medicine.drug |
| Zdroj: | mAbs article-version (VoR) Version of Record mAbs, 12(1):1814661. Landes Bioscience |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | Antibody formation to human(ized) therapeutic antibodies in humans is highly skewed toward anti-idiotype responses, probably because the idiotype is the only ‘foreign’ part of the antibody molecule. Here, we analyzed antibody responses to F(ab’)2 fragments of a panel of 17 human(ized) therapeutic antibodies in rabbits. Homology between the rabbit germline and the human(ized) antibodies is moderate not only for the variable domains (both the complementarity-determining regions and the framework regions), but also for the constant domains (66% or less). Nevertheless, we observed a highly skewed anti-idiotype response in all cases, with up to >90% of the antibodies directed toward the idiotype. These results indicate that the idiotype may be inherently immunodominant. We used these biased responses to raise monoclonal rabbit anti-idiotype antibodies against secukinumab, ustekinumab, reslizumab, mepolizumab, palivizumab, and dupilumab and demonstrate the potential to develop sensitive pharmacokinetic assays with these antibodies. |
| Databáze: | OpenAIRE |
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