Analytical Investigation of Forced Oxidized Anti-VEGF IgG Molecules: A Focus on the Alterations in Antigen and Receptor Binding Activities
Scientia Pharmaceutica, cilt.91, sa.3, 2023 (ESCI, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 91 Sayı: 3
- Basım Tarihi: 2023
- Doi Numarası: 10.3390/scipharm91030031
- Dergi Adı: Scientia Pharmaceutica
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, CAB Abstracts, Chemical Abstracts Core, Chimica, International Pharmaceutical Abstracts, Veterinary Science Database, Directory of Open Access Journals
- Anahtar Kelimeler: monoclonal antibodies, forced degradation studies, oxidative stress
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Alterations in the biological activity of the molecules under stress conditions have not been documented as widely in the literature yet. This study was designed to reveal the functional impacts of various oxidation conditions on a model mAb, a commercial anti-VEGF IgG molecule. The responses to antigen binding, cell proliferation, FcRn receptors, and C1q binding, which rarely appear in the current literature, were investigated. The authors report peptide mapping data, post-translational modification (PTM) analysis, cell proliferation performance, and antigen (VEGF), C1q, and FcRn binding activities of the mAb under various stress conditions. The oxidation-prone site of the mAb was determined as Met252 in the DTLMISR peptide. The VEGF binding activity and anti-cell proliferation activity of the mAbs did not alter, while C1q and FcRn binding capacity significantly decreased under oxidative stress conditions. The full report is vital for many scientific and industrial processes about mAbs. The authors recommend performing functional analyses in addition to the structural studies while investigating the impacts of stress factors on therapeutic mAbs.