Binding, Neutralization and Internalization of the Interleukin-13 Antibody, Lebrikizumab

Autor: Angela J. Okragly, Aya Ryuzoji, Isabella Wulur, Montanea Daniels, Robert D. Van Horn, Chetan N. Patel, Robert J. Benschop
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Dermatology and Therapy, Vol 13, Iss 7, Pp 1535-1547 (2023)
Druh dokumentu: article
ISSN: 2193-8210
2190-9172
DOI: 10.1007/s13555-023-00947-7
Popis: Abstract Introduction IL-13 is the primary upregulated cytokine in atopic dermatitis (AD) skin and is the pathogenic mediator driving AD pathophysiology. Lebrikizumab, tralokinumab and cendakimab are therapeutic monoclonal antibodies (mAb) that target IL-13. Methods We undertook studies to compare in vitro binding affinities and cell-based functional activities of lebrikizumab, tralokinumab and cendakimab. Results Lebrikizumab bound IL-13 with higher affinity (as determined using surface plasma resonance) and slower off-rate. It was more potent in neutralizing IL-13-induced effects in STAT6 reporter and primary dermal fibroblast periostin secretion assays than either tralokinumab or cendakimab. Live imaging confocal microscopy was employed to determine the mAb effects on IL-13 internalization into cells via the decoy receptor IL-13Rα2, using A375 and HaCaT cells. The results showed that only the IL-13/lebrikizumab complex was internalized and co-localized with lysosomes, whereas IL-13/tralokinumab or IL-13/cendakimab complexes did not internalize. Conclusion Lebrikizumab is a potent, neutralizing high-affinity antibody with a slow disassociation rate from IL-13. Additionally, lebrikizumab does not interfere with IL-13 clearance. Lebrikizumab has a different mode of action to both tralokinumab and cendakimab, possibly contributing to the clinical efficacy observed by lebrikizumab in Ph2b/3 AD studies.
Databáze: Directory of Open Access Journals
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