GingisKHAN™ protease cleavage allows a high-throughput antibody to Fab conversion enabling direct functional assessment during lead identification of human monoclonal and bispecific IgG1 antibodies

References

• Porter RR. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959;73:119-26. PMID:14434282
   PubMed Web of Science ®Google Scholar
• Mage M, Lamoyi E. Preparation of Fab and F(ab’) fragments from monoclonal antibodies. In: Schook LB, editor. Monoclonal antibody production techniques and applications. New York (US): Marcel Dekker Inc; 1987. p. 79-97
   Google Scholar
• Akita EM, Nakai S. Production and purification of Fab' fragments from chicken egg yolk immunoglobulin Y (IgY). J Immunol Methods 1993; 162(2):155-64. PMID:8315286
   PubMed Web of Science ®Google Scholar
• Andrew SM, Titus JA. Fragmentation of Immunoglobulin G. Curr Protocols Cell Biol. Hoboken, New Jersey, USA: John Wiley & Sons Inc; 2003. p. 16.4.1-16.4.10. doi:10.1002/0471143030.cb1604s17. PMID:18228421
   PubMedGoogle Scholar
• Zhao Y, Gutshall L, Jiang H, Baker A, Beil E, Obmolova G, Carton J, Taudte S, Amegadzie B. Two routes for production and purification of Fab fragments in biopharmaceutical discovery research: Papain digestion of mAb and transient expression in mammalian cells. Protein Expr Purif. 2009;67(2):182-89. doi:10.1016/j.pep.2009.04.012. PMID:19442740
   PubMed Web of Science ®Google Scholar
• Parham P. On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b from BALB/c mice. J Immunol. 1983;131(6):2895-902. PMID:6358356
   PubMed Web of Science ®Google Scholar
• Parham P. Preparation and purification of active fragments from mouse monoclonal antibodies. In: Weir DM, editor. Handbook of Experimental Immunology. Oxford (UK): Blackwell Scientific Publications; fourth ed; 1986. p. 14.1-14.23
   Google Scholar
• Tischer W, Kasche V. Immobilized enzymes: crystals or carriers? Trends Biotechnol. 1999;17(8):326-35. PMID:10407405
   PubMed Web of Science ®Google Scholar
• Luo Q, Mao X, Kong L, Huang X, Zou H. High-performance affinity chromatography for characterization of human immunoglobulin G digestion with papain. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;776(2):139-47. PMID:12137995
   PubMed Web of Science ®Google Scholar
• Gadgil HS, Bondarenko PV, Pipes GD, Dillon TM, Banks D, Abel J, Kleemann GR, Treuheit MJ. Identification of cysteinylation of a free cysteine in the Fab region of a recombinant monoclonal IgG1 antibody using Lys-C limited proteolysis coupled with LC/MS analysis. Anal Biochem. 2006;355(2):165-74. doi:10.1016/j.ab.2006.05.037. PMID:16828048
   PubMed Web of Science ®Google Scholar
• von Pawel-Rammingen U, Johansson BP, Björck L. IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. EMBO J. 2002;21(7):1607-15. doi:10.1093/emboj/21.7.1607. PMID:11927545
   PubMed Web of Science ®Google Scholar
• von Pawel-Rammingen U, Björck L. IdeS and SpeB: immunoglobulin-degrading cysteine proteinases of Streptococcus pyogenes. Curr Opin Microbiol. 2003;6(1):50-5. PMID:12615219
   PubMed Web of Science ®Google Scholar
• Ishikawa E, Yoshitake S. A general and mild procedure for the purification of rabbit Fab' antibodies. J Immunol Methods. 1980;38(1–2):117-23. PMID:7452000
   PubMed Web of Science ®Google Scholar
• Billah MM, Hodges CS, Hays HC, Millner PA. Directed immobilization of reduced antibody fragments onto a novel SAM on gold for myoglobin impedance immunosensing. Bioelectrochemistry. 2010;80(1):49-54. doi:10.1016/j.bioelechem.2010.08.005. PMID:20880761
   PubMed Web of Science ®Google Scholar
• DeSilva BS, Wilson GS. Solid phase synthesis of bifunctional antibodies. J Immunol Methods. 1995;188(1):9-19. PMID:8551042
   PubMed Web of Science ®Google Scholar
• Makaraviciute A, Jackson CD, Millner PA, Ramanaviciene A. Considerations in producing preferentially reduced half-antibody fragments. J Immunol Methods. 2016;429:50-6. doi:10.1016/j.jim.2016.01.001. PMID:26779832
   PubMed Web of Science ®Google Scholar
• Scott CF, Whitaker EJ, Hammond BF, Colman RW. Purification and characterization of a potent 70-kDa thiol lysyl-proteinase (Lys-gingivain) from Porphyromonas gingivalis that cleaves kininogens and fibrinogen. J Biol Chem. 1993;268(11):7935-42. PMID:8385128
   PubMed Web of Science ®Google Scholar
• Okamoto K, Kadowaki T, Nakayama K, Yamamoto K. Cloning and sequencing of the gene encoding a novel lysine-specific cysteine proteinase (Lys-gingipain) in Porphyromonas gingivalis: structural relationship with the arginine-specific cysteine proteinase (Arg-gingipain). J Biochem. 1996;120(2):398-406. PMID:8889827
   PubMed Web of Science ®Google Scholar
• Fujimura S, Hirai K, Shibata Y, Nakayama K, Nakamura T. Comparative properties of envelope-associated arginine-gingipains and lysine-gingipain of Porphyromonas gingivalis. FEMS Microbiol Lett. 1998;163(2):173-9. PMID:9673019
   PubMed Web of Science ®Google Scholar
• Vincents B, Guentsch A, Kostolowska D, von Pawel-Rammingen U, Eick S, Potempa J, Abrahamson M. Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis. FASEB J. 2011;25(10):3741-50. doi:10.1096/fj.11-187799. PMID:21768393
   PubMed Web of Science ®Google Scholar
• Genovis AB. Lund: Sweden. https://www.genovis.com/products/gingiskhan/
   Google Scholar
• 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. PMID:27285945
   PubMed Web of Science ®Google Scholar
• Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161(2):851-8. PMID:2735925
   PubMed Web of Science ®Google Scholar
• Davis S, Papadopoulos N, Aldrich TH, Maisonpierre PC, Huang T, Kovac L, Xu A, Leidich R, Radziejewska E, Rafique A, et al. Angiopoietins have distinct modular domains essential for receptor binding, dimerization and superclustering. Nat Struct Biol. 2003;10(1):38-44. doi:10.1038/nsb880. PMID:12469114
   PubMedGoogle Scholar
• Lisowska E, Krop-Watorek A, Sedlaczek P. The dimeric structure of carcinoembryonic antigen (CEA). Biochem Biophys Res Commun. 1983;115(1):206-11. PMID:6615527
   PubMed Web of Science ®Google Scholar
• Barton WA, Tzvetkova D, Nikolov DB. Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition. Structure. 2005;13(5):825-32. doi:10.1016/j.str.2005.03.009. PMID:15893672
   PubMed Web of Science ®Google Scholar
• Aertgeerts K, Levin I, Shi L, Snell GP, Jennings A, Prasad GS, Zhang Y, Kraus ML, Salakian S, Sridhar V, et al. Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha. J Biol Chem. 2005;280(20):19441-4. doi:10.1074/jbc.C500092200. PMID:15809306
   PubMed Web of Science ®Google Scholar
• Schaefer W, Regula JT, Bähner M, Schanzer J, Croasdale R, Dürr H, Gassner C, Georges G, Kettenberger H, Imhof-Jung S, et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc Natl Acad Sci U S A. 2011;108(27):11187-92. doi:10.1073/pnas.1019002108. PMID:21690412
   PubMed Web of Science ®Google Scholar
• Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today 2015;20(7):838-47. doi:10.1016/j.drudis.2015.02.008. PMID:25728220
   PubMed Web of Science ®Google Scholar
• Spiess C, Zhai Q, Carter PJ. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol. 2015;67(2 Pt A):95-106. doi:10.1016/j.molimm.2015.01.003. PMID:25637431
   PubMed Web of Science ®Google Scholar
• Kovari LC, Momany C, Rossmann MG. The use of antibody fragments for crystallization and structure determinations. Structure. 1995;3(12):1291-3. PMID:8747455
   PubMed Web of Science ®Google Scholar