دورية أكاديمية
Harnessing ceramic hydroxyapatite as an effective polishing strategy to remove product- and process-related impurities in bispecific antibody purification.
| العنوان: | Harnessing ceramic hydroxyapatite as an effective polishing strategy to remove product- and process-related impurities in bispecific antibody purification. |
|---|---|
| المؤلفون: | Ingavat N; Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Wang X; Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Liew JM; Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Mahfut FB; Cell Line Development Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., But KP; Protein Analytics Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Kok YJ; Protein Analytics Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Bi X; Protein Analytics Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Yang Y; Cell Line Development Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Shintaro K; Chromatography Media Business Division, HOYA Technosurgical Corporation, Singapore Branch, Singapore., Tsoumpra M; Chromatography Media Business Division, HOYA Technosurgical Corporation, Singapore Branch, Singapore., Zhang W; Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. zhang_wei@bti.a-star.edu.sg. |
| المصدر: | Bioresources and bioprocessing [Bioresour Bioprocess] 2023 Dec 13; Vol. 10 (1), pp. 93. Date of Electronic Publication: 2023 Dec 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer-Verlag, GmbH Country of Publication: Germany NLM ID: 101665551 Publication Model: Electronic Cited Medium: Internet ISSN: 2197-4365 (Electronic) Linking ISSN: 21974365 NLM ISO Abbreviation: Bioresour Bioprocess Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Heidelberg, Germany : Springer-Verlag, GmbH, [2014]- |
| مستخلص: | Bispecific antibody (bsAb), a novel therapeutic modality, provides excellent treatment efficacy, yet poses numerous challenges to downstream process development, which are mainly due to the intricate diversity of bsAb structures and impurity profiles. Ceramic hydroxyapatite (CHT), a mixed-mode medium, allows proteins to interact with its calcium sites (C-sites) through metal affinity and/or its phosphate sites (P-sites) through cation exchange interactions. This dual-binding capability potentially offers unique bind and elute behaviours for different proteins of interest, resulting in optimal product purity when suitable elution conditions are employed. In this study, the effectiveness of CHT as a polishing step for bsAb purification was investigated across three model molecules and benchmarked against the traditional cation exchange chromatography (CEX). For both asymmetric and symmetric IgG-like bsAb post Protein A eluates, at least 97% product purity was achieved after CHT polishing. CHT delivered a superior aggregate clearance to CEX, resulting in low high molecular weight (HMW) impurities (0.5%) and low process-related impurities in the product pools. Moreover, CHT significantly mitigated "chromatography-induced aggregation" whereas eightfold more HMW was generated by CEX. This study illustrated the developability of CHT in effectively eliminating low molecular weight (LMW) impurities through post-load-wash (PLW) optimization, resulting in an additional reduction of up to 48% in LMW impurities. A mechanistic explanation regarding the performance of impurity removal and mitigation of the chromatography-induced aggregation by CHT was proposed, illustrating unique CHT capability is potentially driven by C-site cooperation, of which effectiveness could depend on the bsAb composition and size. (© 2023. The Author(s).) |
| References: | MAbs. 2020 Jan-Dec;12(1):1718440. (PMID: 31983280) J Chromatogr A. 2019 Sep 13;1601:121-132. (PMID: 31056270) J Chromatogr A. 2014 Oct 3;1362:186-93. (PMID: 25182858) N Biotechnol. 2009 Jun;25(5):287-93. (PMID: 19491046) Anal Chem. 2011 May 15;83(10):3709-16. (PMID: 21495696) J Sep Sci. 2009 Nov;32(22):3857-65. (PMID: 19877136) Protein Expr Purif. 2017 Jun;134:96-103. (PMID: 28414067) J Chromatogr A. 2020 Jan 4;1609:460504. (PMID: 31500880) MAbs. 2021 Jan-Dec;13(1):1967714. (PMID: 34491877) Nat Biotechnol. 1998 Jul;16(7):677-81. (PMID: 9661204) Anal Biochem. 1984 Feb;136(2):425-32. (PMID: 6721142) Nat Rev Drug Discov. 2019 Aug;18(8):585-608. (PMID: 31175342) Anal Biochem. 1984 Feb;136(2):433-9. (PMID: 6721143) MAbs. 2017 Feb/Mar;9(2):257-268. (PMID: 27937066) Antib Ther. 2021 May 07;4(2):73-88. (PMID: 34056544) Int J Pharm. 2020 Jul 30;585:119523. (PMID: 32531452) Curr Protein Pept Sci. 2019;20(1):75-81. (PMID: 29065831) MAbs. 2016 May-Jun;8(4):828-38. (PMID: 26963837) J Chromatogr A. 2020 Oct 11;1629:461465. (PMID: 32827903) Curr Opin Biotechnol. 2018 Oct;53:59-64. (PMID: 29278833) J Chromatogr A. 2019 Feb 22;1587:136-145. (PMID: 30587350) Pharmacol Ther. 2018 Feb;182:161-175. (PMID: 28834699) Nat Biotechnol. 2014 Feb;32(2):136-7. (PMID: 24509759) Front Immunol. 2022 Oct 28;13:1035276. (PMID: 36389699) Anal Biochem. 1984 Feb;136(2):440-5. (PMID: 6721144) J Immunol Methods. 1993 Jun 18;162(2):201-10. (PMID: 8391046) Antibodies (Basel). 2016 Sep 05;5(3):. (PMID: 31558000) Protein Eng. 1996 Jul;9(7):617-21. (PMID: 8844834) Protein Cell. 2018 Jan;9(1):63-73. (PMID: 28986820) Biotechnol Bioeng. 2015 Nov;112(11):2292-304. (PMID: 25950654) Biotechnol J. 2012 Jan;7(1):90-102. (PMID: 22147583) J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Jan 15;975:1-8. (PMID: 25462105) J Chromatogr A. 1998 Feb 13;796(1):165-75. (PMID: 9513290) |
| فهرسة مساهمة: | Keywords: Bispecific antibody; Chromatography-induced aggregation; Mixed-mode chromatography; Product- and process-related impurity removal |
| تواريخ الأحداث: | Date Created: 20240422 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| مُعرف محوري في PubMed: | PMC10992335 |
| DOI: | 10.1186/s40643-023-00713-9 |
| PMID: | 38647984 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2197-4365 |
|---|---|
| DOI: | 10.1186/s40643-023-00713-9 |