Temperature and pH-dependent behaviors of mAb drugs: A case study for trastuzumab

Sert, Fatma; Hız, Defne; Gülmez, Mert; Cankurtaran, Selen Ezgi; Kayalan, Cemre Irmak; Kurt, Hasan; Yüce, Meral

Temperature and pH-dependent behaviors of mAb drugs: A case study for trastuzumab

dc.authorid	0000-0002-1677-644X
dc.contributor.author	Sert, Fatma
dc.contributor.author	Hız, Defne
dc.contributor.author	Gülmez, Mert
dc.contributor.author	Cankurtaran, Selen Ezgi
dc.contributor.author	Kayalan, Cemre Irmak
dc.contributor.author	Kurt, Hasan
dc.contributor.author	Yüce, Meral
dc.date.accessioned	2022-04-14T07:23:50Z
dc.date.available	2022-04-14T07:23:50Z
dc.date.issued	2022
dc.department	İstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümü
dc.department	İstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.description.abstract	The distortions in the high-order structure of therapeutic monoclonal antibodies (mAbs) under different environmental conditions acutely affect mAb stability, resulting in altered safety, efficacy, and shelf-life profiles. The overall stability of mAbs depends on many factors, and it requires complementary techniques for an in-depth analysis. The stability of mAbs can be characterized by differential centrifugal sedimentation (DCS), differential scanning calorimetry (DSC), differential scanning fluorimetry (DSF), and size exclusion chromatography (SEC) techniques. In this report, temperature-ramped dynamic light scattering (DLS), and circular dichroism (CD) spectroscopy were employed as complementary tools to show how temperature and pH affect the aggregation of a model mAb, trastuzumab, in solution. The results showed that the aggregation onset temperature of trastuzumab defined by DLS was 75 degrees C, which decreases the amount of beta-sheets and causes a slight increase in helix structures. Moreover, the melting temperature of trastuzumab was determined to be between 80-83 degrees C by temperature-ramped CD spectrophotometry, which is in line with the Tm of trastuzumab's Fab region tested with DSC. Thus, unfolding and aggregation of trastuzumab start simultaneously at 75 degrees C, and unfolding triggers the aggregation. The temperature-ramped CD and DLS methods are robust tools to determine the thermal behavior of biosimilars in various solution conditions. Their complementary usage provides solid scientific background for regulatory applications and a better understanding of mAb instability and its relationship with structural changes.
dc.identifier.citation	Sert, F., Hız, D., Gülmez, M., Cankurtaran, S. E., Kayalan, C. I., Kurt, H. ... Yüce, M. (2022). Temperature and pH-dependent behaviors of mAb drugs: A case study for trastuzumab. Scientia Pharmaceutica, 90(1). https://doi.org/10.3390/scipharm90010021
dc.identifier.doi	10.3390/scipharm90010021
dc.identifier.issn	2218-0532
dc.identifier.issue	1
dc.identifier.scopus	2-s2.0-85128075251
dc.identifier.scopusquality	Q2
dc.identifier.uri	https://doi.org/10.3390/scipharm90010021
dc.identifier.uri	https://hdl.handle.net/20.500.12511/9334
dc.identifier.volume	90
dc.identifier.wos	000774348500001	en_US
dc.identifier.wosquality	N/A
dc.indekslendigikaynak	Web of Science
dc.indekslendigikaynak	Scopus
dc.institutionauthor	Kurt, Hasan
dc.language.iso	en
dc.publisher	MDPI
dc.relation.ispartof	Scientia Pharmaceutica	en_US
dc.relation.publicationcategory	Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitak	info:eu-repo/grantAgreement/TUBITAK/SOBAG/2244
dc.rights	Attribution 4.0 International	*
dc.rights	https://creativecommons.org/licenses/by/4.0/	*
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Thermal Stability
dc.subject	Conformational Stability
dc.subject	Colloidal Stability
dc.subject	Biophysical Characterization
dc.subject	Complementary Tools
dc.title	Temperature and pH-dependent behaviors of mAb drugs: A case study for trastuzumab
dc.type	Article