3,615
Views
3
CrossRef citations to date
0
Altmetric
Report

Characterization of high-molecular weight by-products in the production of a trivalent bispecific 2+1 heterodimeric antibody

, , , , , , & show all
Article: 2175312 | Received 10 Oct 2022, Accepted 29 Jan 2023, Published online: 17 Feb 2023

References

  • Wang S, Chen K, Lei Q, Ma P, Yuan AQ, Zhao Y, Jiang Y, Fang H, Xing S, Fang Y, et al. The state of the art of bispecific antibodies for treating human malignancies. EMBO Mol Med. 2021;13(9):e14291. doi:10.15252/emmm.202114291.
  • The Antibody Society. Therapeutic monoclonal antibodies approved or in regulatory review. (Accessed Jan. 27, 2023); www.antibodysociety.org/antibody-therapeutics-product-data
  • Kontermann R. Dual targeting strategies with bispecific antibodies. MAbs. 2012;4(2):182–13. doi:10.4161/mabs.4.2.19000.
  • Sheridan C. Bispecific antibodies poised to deliver wave of cancer therapies. Nat Biotechnol. 2021;39(3):251–54. doi:10.1038/s41587-021-00850-6.
  • Suurs FV, Lub-de Hooge MN, de Vries EGE, de Groot DJA. A review of bispecific antibodies and antibody constructs in oncology and clinical challenges. Pharmacol Ther. 2019;201:103–19. doi:10.1016/j.pharmthera.2019.04.006.
  • Brinkmann U, Kontermann RE. The making of bispecific antibodies. MAbs. 2017;9(2):182–212. doi:10.1080/19420862.2016.1268307.
  • Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18(8):585–608. doi:10.1038/s41573-019-0028-1.
  • Chiu ML, Gilliland GL. Engineering antibody therapeutics. Curr Opin Struct Biol. 2016;38:163–73. doi:10.1016/j.sbi.2016.07.012.
  • Diederich P, Hansen SK, Oelmeier SA, Stolzenberger B, Hubbuch J. A sub-two minutes method for monoclonal antibody-aggregate quantification using parallel interlaced size exclusion high performance liquid chromatography. J Chromatogr A. 2011;1218(50):9010–18. doi:10.1016/j.chroma.2011.09.086.
  • Klein C, Schaefer W, Regula JT. The use of CrossMAb technology for the generation of bi- and multispecific antibodies. MAbs. 2016;8(6):1010–20. doi:10.1080/19420862.2016.1197457.
  • Bacac M, Klein C, Cea Tcb: UP. A novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. Oncoimmunology. 2016;5(8):8–10. doi:10.1080/2162402X.2016.1203498.
  • Lu C, Liu D, Liu H, Motchnik P. Characterization of monoclonal antibody size variants containing extra light chains. MAbs. 2013;5(1):102–13. doi:10.4161/mabs.22965.
  • Haberger M, Leiss M, Heidenreich AK, Pester O, Hafenmair G, Hook M, Haindl M, Reusch D, Bulau P, Reusch D. Rapid characterization of biotherapeutic proteins by size-exclusion chromatography coupled to native mass spectrometry. MAbs. 2016;8(2):331–39. doi:10.1080/19420862.2015.1122150.
  • Todoroki K, Mizuno H, Sugiyama E, Toyo’Oka T. Bioanalytical methods for therapeutic monoclonal antibodies and antibody–drug conjugates: a review of recent advances and future perspectives. J Pharm Biomed Anal. 2020;179:112991. doi:10.1016/j.jpba.2019.112991.
  • Rosati S, Yang Y, Barendregt A, Heck AJR. Detailed mass analysis of structural heterogeneity in monoclonal antibodies using native mass spectrometry. Nat Protoc. 2014;9(4):967–76. doi:10.1038/nprot.2014.057.
  • Beck A, Sanglier-Cianférani S, Van Dorsselaer A. Biosimilar, biobetter, and next generation antibody characterization by mass spectrometry. Anal Chem. 2012;84(11):4637–46. doi:10.1021/ac3002885.
  • Thompson NJ, Hendriks LJA, De Kruif J, Throsby M, Heck AJR. Complex mixtures of antibodies generated from a single production qualitatively and quantitatively evaluated by native Orbitrap mass spectrometry. MAbs. 2014;6(1):197–203. doi:10.4161/mabs.27126.
  • Phung W, Han G, Polderdijk SGI, Dillon M, Shatz W, Liu P, Wei B, Suresh P, Fischer D, Spiess C, et al. Data on charge separation of bispecific and mispaired IgGs using native charge-variant mass spectrometry. Data Br. 2020;30:105435. doi:10.1016/j.dib.2020.105435.
  • Schachner L, Han G, Dillon M, Zhou J, McCarty L, Ellerman D, Yin Y, Spiess C, Lill J, Carter PJ, et al. Characterization of chain pairing variants of bispecific IgG expressed in a single host cell by high-resolution native and denaturing mass spectrometry. Anal Chem. 2016;88(24):12122–27. doi:10.1021/acs.analchem.6b02866.
  • Kükrer B, Filipe V, Van Duijn E, Kasper PT, Vreeken RJ, Heck AJR, Jiskoot W. Mass spectrometric analysis of intact human monoclonal antibody aggregates fractionated by size-exclusion chromatography. Pharm Res. 2010;27(10):2197–204. doi:10.1007/s11095-010-0224-5.
  • Haberger M, Heidenreich AK, Schlothauer T, Hook M, Gassner J, Bomans K, Yegres M, Zwick A, Zimmerman B, Wegele H, et al. Functional assessment of antibody oxidation by native mass spectrometry. MAbs. 2015;7(5):891–900. doi:10.1080/19420862.2015.1052199.
  • Rosati S, Van Den Bremer ET, Schuurman J, Parren PW, Kamerling JP, Heck AJ. In-depth qualitative and quantitative analysis of composite glycosylation profiles and other micro-heterogeneity on intact monoclonal antibodies by high-resolution native mass spectrometry using a modified Orbitrap. MAbs. 2013;5(6):917–24. doi:10.4161/mabs.26282.
  • Haberger M, Heidenreich A-K, Hook M, Fichtl J, Lang R, Cymer F, Adibzadeh M, Kuhne F, Wegele H, Reusch D, et al. Multiattribute monitoring of antibody charge variants by cation-exchange chromatography coupled to native mass spectrometry. J Am Soc Mass Spectrom. 2021;32(8):2062–71. Published online. doi:10.1021/jasms.0c00446.
  • Füssl F, Trappe A, Cook K, Scheffler K, Fitzgerald O, Bones J. Comprehensive characterisation of the heterogeneity of Adalimumab via charge variant analysis hyphenated on-line to native high resolution Orbitrap mass spectrometry. MAbs. 2019;11(1):116–28. doi:10.1080/19420862.2018.1531664.
  • Bailey AO, Han G, Phung W, Gazis P, Sutton J, Josephs JL, Sandoval W. Charge variant native mass spectrometry benefits mass precision and dynamic range of monoclonal antibody intact mass analysis. MAbs. 2018;10(8):1214–25. doi:10.1080/19420862.2018.1521131.
  • Yan Y, Xing T, Liu AP, Zhang Z, Wang S. Post-Column Denaturation-Assisted LN. Native size-exclusion chromatography–mass spectrometry for rapid and in-depth characterization of high molecular weight variants in therapeutic monoclonal antibodies. J Am Soc Mass Spectrom. 2021;32(12):2885–94. doi:10.1021/jasms.1c00289.
  • Zhang L, English AM, Bai DL,Ugrin SA, Shabanowits J, Ross MM, Hunt DF, Wang WH. Analysis of monoclonal antibody sequence and post-translational modifications by time-controlled proteolysis and tandem mass spectrometry. Mol Cell Proteomics. 2016;15(4):1479–88. doi:10.1074/mcp.O115.056721.
  • Gavin Y, Nikolas H, Daniel C, Fineberg A, Andrecka J, Tyler A, Olerinyova A, Ansari A, Marklund EG, Collier MP, et al. Quantitative mass imaging of single biological macromolecules. Science. 2018;360(6387):423–27. doi:10.1126/science.aar5839.
  • 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.
  • Ridgway JBB, Presta LG, Carter P. Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng Des Sel. 1996;9(7):617–21. doi:10.1093/protein/9.7.617.
  • Gstöttner C, Reusch D, Haberger M, Dragan I, Veelen PV, Kilgour DPA, Tsybin YO, van der Burgt YEM, Wuhrer M, Nicolardi S. Monitoring glycation levels of a bispecific monoclonal antibody at subunit level by ultrahigh-resolution MALDI FT-ICR mass spectrometry. MAbs. 2020;12(1):1682403. doi:10.1080/19420862.2019.1682403.
  • Lippold S, Hook M, Spick C, Knaupp A, Wang K, Ruperti F, Cadang L, Andersen N, Vogt A, Grote M, et al. CD3 target affinity chromatography mass spectrometry for function-structure characterization of product-related variants. Anal Chem. 2023;95(4):2260–68. Published online.
  • Plath F, Ringler P, Graff-Meyer A, Stahlberg H, Lauer ME, Rufer AC, Grawert MA, Svergun D, Gellerman G, Finkler C, et al. Characterization of mAb dimers reveals predominant dimer forms common in therapeutic mAbs. MAbs. 2016;8(5):928–40. doi:10.1080/19420862.2016.1168960.
  • Deslignière E, Ley M, Bourguet M, Ehkirch A, Botzanowski T, Erb S, Hernandez-Alba O, Cianferani 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.
  • Sjögren J, Olsson F, Beck A. Rapid and improved characterization of therapeutic antibodies and antibody related products using IdeS digestion and subunit analysis. Analyst. 2016;141(11):3114–25. doi:10.1039/C6AN00071A.
  • Xiang T, Lundell E, Sun Z, Liu H. Structural effect of a recombinant monoclonal antibody on hinge region peptide bond hydrolysis. J Chromatogr B, Anal Technol Biomed Life Sci. 2007;858(1–2):254–62. doi:10.1016/j.jchromb.2007.08.043.
  • Luijkx YMCA, Henselijn AJ, Bosman GP, Cramer DAT, Giesbers KCAP, van ‘t Veld EM, Gj B, AJR H, Kr R, Strijbis K, et al. Detection of bacterial α-l-Fucosidases with an Ortho-Quinone methide-based probe and mapping of the probe-protein adducts. Mol. 2022;27(5). doi:10.3390/molecules27051615
  • Franc V, Yang Y, Heck AJR. Proteoform profile mapping of the human serum complement component C9 revealing unexpected new features of N-, O-, and C-Glycosylation. Anal Chem. 2017;89(6):3483–91. doi:10.1021/acs.analchem.6b04527.