T cell epitope mapping of secukinumab and ixekizumab in healthy donors
| Autor: | Thomas Huber, Frank Kolbinger, Maxime Tenon, Evelyne Correia, Bernard Maillere, Sebastian Spindeldreher, Anette Karle, Sascha Gottlieb |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.drug_class T cell Immunology Epitopes T-Lymphocyte immunogenicity Monoclonal antibody Antibodies Monoclonal Humanized 03 medical and health sciences Psoriatic arthritis 0302 clinical medicine ixekizumab Psoriasis Report Immunology and Allergy Medicine Humans Secukinumab 030304 developmental biology 0303 health sciences T cell lines business.industry Immunogenicity Interleukin-17 in vitro medicine.disease Healthy Volunteers Ixekizumab epitope mapping Epitope mapping medicine.anatomical_structure 030220 oncology & carcinogenesis business MAPPs |
| Zdroj: | mAbs article-version (VoR) Version of Record |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | Secukinumab, a human monoclonal antibody that selectively neutralizes IL-17A, has consistently shown low anti-drug antibody responses in patients with psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab has also shown lower in vitro immunogenicity potential compared with other monoclonal antibodies used to treat psoriasis and psoriatic arthritis, and a significantly lower in vitro T cell precursor frequency compared with ixekizumab, which targets the same antigen. Here, secukinumab and ixekizumab were further examined regarding their specific T cell epitopes. Secukinumab- or ixekizumab-specific CD4 T cell lines were generated from 31 healthy, treatment-naïve donors via 28-day co-culture with mature monocyte-derived dendritic cells exposed to either antibody. Consistent with previous data, the frequency of preexisting T cells to secukinumab was significantly lower as compared with ixekizumab. Only two T cell lines from two different donors could be derived for secukinumab, but no specific T cell epitope was identified. In contrast, 32 T cell lines from eight donors were obtained for ixekizumab. For 11 of these T cell lines, the specific T cell epitopes could be identified and confirmed by major histocompatibility complex–associated peptide proteomics as being naturally presented peptides. All identified T cell epitopes cluster in four main regions that are overlapping with the complementarity-determining regions HCDR3, LCDR1, LCDR2 and LCDR3. Interestingly, ixekizumab CDRs contain amino acids that are not found in any of the germline family members. These amino acids may be associated with the higher number of T cell epitopes identified for ixekizumab light chain and may contribute to the increased in vitro immunogenicity potential observed for ixekizumab vs. secukinumab. |
| Databáze: | OpenAIRE |
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