Evaluation of the impact of antibody fragments on aggregation of intact molecules via size exclusion chromatography coupled with native mass spectrometry

References

• Lu R-M, Hwang Y-C, Liu IJ, Lee C-C, Tsai H-Z, Li H-J, Wu H-C. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27(1):1. doi:10.1186/s12929-019-0592-z.
   PubMed Web of Science ®Google Scholar
• Tsumoto K, Isozaki Y, Yagami H, Tomita M. Future perspectives of therapeutic monoclonal antibodies. Immunotherapy. 2019;11(2):119–12. doi:10.2217/imt-2018-0130.
   PubMed Web of Science ®Google Scholar
• Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov. 2010;9(10):767–74. doi:10.1038/nrd3229.
   PubMed Web of Science ®Google Scholar
• Vázquez-Rey M, Lang DA. Aggregates in monoclonal antibody manufacturing processes. Biotechnol Bioeng. 2011;108(7):1494–508. doi:10.1002/bit.23155.
   PubMed Web of Science ®Google Scholar
• Lowe D, Dudgeon K, Rouet R, Schofield P, Jermutus L, Christ D. Aggregation, stability, and formulation of human antibody therapeutics. Adv Protein Chem Struct Biol. 2011;84:41–61.
   PubMed Web of Science ®Google Scholar
• Li W, Prabakaran P, Chen W, Zhu Z, Feng Y, Dimitrov DS. Antibody aggregation: insights from sequence and structure. Antibodies (Basel). 2016;5(3):19. doi:10.3390/antib5030019.
   PubMedGoogle Scholar
• Mahler HC, Friess W, Grauschopf U, Kiese S. Protein aggregation: pathways, induction factors and analysis. J Pharm Sci. 2009;98(9):2909–34. doi:10.1002/jps.21566.
   PubMed Web of Science ®Google Scholar
• Wu H, Kroe-Barrett R, Singh S, Robinson AS, Roberts CJ. Competing aggregation pathways for monoclonal antibodies. FEBS Lett. 2014;588(6):936–41. doi:10.1016/j.febslet.2014.01.051.
   PubMed Web of Science ®Google Scholar
• Gupta S, Jiskoot W, Schöneich C, Rathore AS. Oxidation and deamidation of monoclonal antibody products: potential impact on stability, biological activity, and efficacy. J Pharm Sci. 2021;111(4):903–18. doi:10.1016/j.xphs.2021.11.024.
   PubMed Web of Science ®Google Scholar
• Chennamsetty N, Voynov V, Kayser V, Helk B, Trout BL. Prediction of aggregation prone regions of therapeutic proteins. J Phys Chem B. 2010;114(19):6614–24. doi:10.1021/jp911706q.
   PubMed Web of Science ®Google Scholar
• Dindo M, Conter C, Cellini B. Electrostatic interactions drive native-like aggregation of human alanine: glyoxylate aminostransferase. FEBS J. 2017;284(21):3739–64. doi:10.1111/febs.14269.
   PubMed Web of Science ®Google Scholar
• Shah DD, Zhang J, Maity H, Mallela KMG. Effect of photo-degradation on the structure, stability, aggregation, and function of an IgG1 monoclonal antibody. Int J Pharm. 2018;547(1–2):438–49. doi:10.1016/j.ijpharm.2018.06.007.
   PubMed Web of Science ®Google Scholar
• Gaza-Bulseco G, Liu H. Fragmentation of a recombinant monoclonal antibody at various pH. Pharm Res. 2008;25(8):1881–90. doi:10.1007/s11095-008-9606-3.
   PubMed Web of Science ®Google Scholar
• Roberts CJ. Therapeutic protein aggregation: mechanisms, design, and control. Trends Biotechnol. 2014;32(7):372–80. doi:10.1016/j.tibtech.2014.05.005.
   PubMed Web of Science ®Google Scholar
• Vlasak J, Ionescu R. Fragmentation of monoclonal antibodies. Mabs-austin. 2011;3(3):253–63. doi:10.4161/mabs.3.3.15608.
   PubMed Web of Science ®Google Scholar
• Nelson AD, Hoffmann MM, Parks CA, Dasari S, Schrum AG, Gil D. IgG fab fragments forming bivalent complexes by a conformational mechanism that is reversible by osmolytes. J Biol Chem. 2012;287(51):42936–50. doi:10.1074/jbc.M112.410217.
   PubMed Web of Science ®Google Scholar
• Gil D, Schrum AG. Strategies to stabilize compact folding and minimize aggregation of antibody-based fragments. Adv Biosci Biotechnol. 2013;4(4):73–84. doi:10.4236/abb.2013.44A011.
   PubMedGoogle Scholar
• Chakroun N, Hilton D, Ahmad SS, Platt GW, Dalby PA. Mapping the Aggregation Kinetics of a therapeutic antibody fragment. Mol Pharm. 2016;13(2):307–19. doi:10.1021/acs.molpharmaceut.5b00387.
   PubMedGoogle Scholar
• Zhang H, Dalby PA. Stability enhancement in a mAb and fab coformulation. Sci Rep. 2020;10(1):21129. doi:10.1038/s41598-020-77989-w.
   PubMed Web of Science ®Google Scholar
• den Engelsman J, Garidel P, Smulders R, Koll H, Smith B, Bassarab S, Seidl A, Hainzl O, Jiskoot W. Strategies for the assessment of protein aggregates in pharmaceutical biotech product development. Pharm Res. 2011;28(4):920–33. doi:10.1007/s11095-010-0297-1.
   PubMed Web of Science ®Google Scholar
• Beck A, Wagner-Rousset E, Ayoub D, Van Dorsselaer A, Sanglier-Cianférani S. Characterization of therapeutic antibodies and related products. Anal Chem. 2013;85(2):715–36. doi:10.1021/ac3032355.
   PubMed Web of Science ®Google Scholar
• Some D, Amartely H, Tsadok A, Lebendiker M. Characterization of proteins by Size-Exclusion Chromatography coupled to Multi-Angle Light Scattering (SEC-MALS). J Vis Exp. 2019;20(148):e59615. doi:10.3791/59615-v.
   Google Scholar
• Podzimek S. Light scattering, size exclusion chromatography and asymmetric flow field flow fractionation: powerful tools for the characterization of polymers, proteins and nanoparticles. John Wiley & Sons; 2011.
   Google Scholar
• Kaszuba M, Connah MT. Protein and nanoparticle characterisation using light scattering techniques. Part Part Syst Charact. 2006;23(2):193–96. doi:10.1002/ppsc.200601030.
   Web of Science ®Google Scholar
• Tamara S, den Boer MA, Heck AJR. High-resolution native Mass spectrometry. Chem Rev. 2022;122(8):7269–326. doi:10.1021/acs.chemrev.1c00212.
   PubMed Web of Science ®Google Scholar
• den Boer MA, Lai S-H, Xue X, van Kampen MD, Bleijlevens B, Heck AJR. Comparative Analysis of Antibodies and heavily glycosylated macromolecular immune complexes by size-exclusion chromatography multi-angle light scattering, native charge detection mass spectrometry, and mass photometry. Anal Chem. 2022;94(2):892–900. doi:10.1021/acs.analchem.1c03656.
   PubMed Web of Science ®Google Scholar
• Muneeruddin K, Thomas JJ, Salinas PA, Kaltashov IA. Characterization of Small Protein Aggregates and oligomers using size exclusion chromatography with online detection by native electrospray ionization Mass spectrometry. Anal Chem. 2014;86(21):10692–99. doi:10.1021/ac502590h.
   PubMed Web of Science ®Google Scholar
• Yan Y, Xing T, Wang S, Daly TJ, Li N. Coupling Mixed-Mode Size Exclusion Chromatography with native Mass spectrometry for sensitive detection and quantitation of homodimer impurities in Bispecific IgG. Anal Chem. 2019;91(17):11417–24. doi:10.1021/acs.analchem.9b02793.
   PubMed Web of Science ®Google Scholar
• Jones J, Pack L, Hunter JH, Valliere-Douglass JF. Native size-exclusion chromatography-mass spectrometry: suitability for antibody–drug conjugate drug-to-antibody ratio quantitation across a range of chemotypes and drug-loading levels. Mabs-austin. 2020;12(1):1682895. doi:10.1080/19420862.2019.1682895.
   PubMed Web of Science ®Google Scholar
• Deslignière E, Ehkirch A, Botzanowski T, Beck A, Hernandez-Alba O, Cianférani S. Toward automation of collision-induced unfolding experiments through online size exclusion chromatography coupled to native Mass spectrometry. Anal Chem. 2020;92(19):12900–08. doi:10.1021/acs.analchem.0c01426.
   PubMed Web of Science ®Google Scholar
• Deslignière E, Ley M, Bourguet M, Ehkirch A, Botzanowski T, Erb S, Hernandez-Alba O, Cianférani S. Pushing the limits of native MS: online SEC-native MS for structural biology applications. Int J Mass Spectrom. 2021;461:116502. doi:10.1016/j.ijms.2020.116502.
   Web of Science ®Google Scholar
• Ren C, Bailey AO, VanderPorten E, Oh A, Phung W, Mulvihill MM, Harris SF, Liu Y, Han G, Sandoval W. et al. Quantitative determination of protein–ligand affinity by size exclusion chromatography directly coupled to high-resolution native Mass spectrometry. Anal Chem. 2019;91(1):903–11. doi:10.1021/acs.analchem.8b03829.
   PubMed Web of Science ®Google Scholar
• Hernandez-Alba O, Ehkirch A, Beck A, Cianférani S. Analysis of ADCs by native Mass spectrometry. In: Tumey L. editor Antibody-drug conjugates: methods and protocols. New York, NY: Springer US; 2020. pp. 197–211.
   Google Scholar
• Deslignière E, Ehkirch A, Duivelshof BL, Toftevall H, Sjögren J, Guillarme D, D’Atri V, Beck A, Hernandez-Alba O, Cianférani S. et al. State-of-the-art native Mass spectrometry and ion mobility methods to monitor homogeneous site-specific Antibody-Drug Conjugates Synthesis. Pharmaceuticals. 2021;14(6):498. doi:10.3390/ph14060498.
   Web of Science ®Google Scholar
• Xu C-F, Xu J, Sosic Z, Yeung B. Aggregate and fragment analysis in Therapeutic Monoclonal Antibodies Using On-Line Size-Exclusion Chromatography with native Mass spectrometry. LCGC Suppl. 2020;18:18–22, 4.
   Google Scholar
• Haberger M, Leiss M, Heidenreich A-K, Pester O, Hafenmair G, Hook M, Bonnington L, Wegele H, Haindl M, Reusch D. et al. Rapid characterization of biotherapeutic proteins by size-exclusion chromatography coupled to native mass spectrometry. Mabs-austin. 2016;8(2):331–39. doi:10.1080/19420862.2015.1122150.
   PubMed Web of Science ®Google Scholar
• McKay AR, Ruotolo BT, Ilag LL, Robinson CV. Mass measurements of increased accuracy resolve heterogeneous populations of intact ribosomes. J Am Chem Soc. 2006;128(35):11433–42. doi:10.1021/ja061468q.
   PubMed Web of Science ®Google Scholar
• Wang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. J Pharm Sci. 2007;96(1):1–26. doi:10.1002/jps.20727.
   PubMed Web of Science ®Google Scholar
• Zheng K, Bantog C, Bayer R. The impact of glycosylation on monoclonal antibody conformation and stability. Mabs-austin. 2011;3(6):568–76. doi:10.4161/mabs.3.6.17922.
   PubMed Web of Science ®Google Scholar
• Kayser V, Chennamsetty N, Voynov V, Forrer K, Helk B, Trout BL. Glycosylation influences on the aggregation propensity of therapeutic monoclonal antibodies. Biotechnol J. 2011;6(1):38–44. doi:10.1002/biot.201000091.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Qiu H. The mechanistic impact of N-Glycosylation on stability, pharmacokinetics, and immunogenicity of therapeutic proteins. J Pharm Sci. 2019;108(4):1366–77. doi:10.1016/j.xphs.2018.11.029.
   PubMed Web of Science ®Google Scholar
• Wada R, Matsui M, Kawasaki N. Influence of N-glycosylation on effector functions and thermal stability of glycoengineered IgG1 monoclonal antibody with homogeneous glycoforms. Mabs-austin. 2019;11(2):350–72. doi:10.1080/19420862.2018.1551044.
   PubMed Web of Science ®Google Scholar