Heavy and light chain pairing of bivalent quadroma and knobs-into-holes antibodies analyzed by UHR-ESI-QTOF mass spectrometry

References

• Riethmüller G. Symmetry breaking: bispecific antibodies, the beginnings, and 50 years on. Cancer Immun 2012; 12:12; PMID:22896757
   PubMedGoogle Scholar
• Kontermann RE. Dual targeting strategies with bispecific antibodies. Mabs 2012; 4:182-97; PMID:22453100; http://dx.doi.org/10.4161/mabs.4.2.19000
   PubMed Web of Science ®Google Scholar
• Spiess C, Zhai Q, Carter PJ. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol 2015; 67:95-106; PMID:25637431; http://dx.doi.org/10.1016/j.molimm.2015.01.003
   PubMed Web of Science ®Google Scholar
• Milstein C, Cuello AC. Hybrid hybridomas and their use in immunohistochemistry. Nature 1983; 305:537-40; PMID:6137772; http://dx.doi.org/10.1038/305537a0
   PubMed Web of Science ®Google Scholar
• Suresh MR, Cuello AC, Milstein C. Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays. Proc Natl Acad Sci U S A 1986; 83:7989-93; PMID:2429324; http://dx.doi.org/10.1073/pnas.83.20.7989
   PubMed Web of Science ®Google Scholar
• Moldenhauer G. Bispecific antibodies from hybrid hybridoma. In: Kontermann RE (ed.), Bispecific Antibodies, Springer-Verlag Berlin Heidelberg 2011:29-46
   Google Scholar
• Lindhofer H, Mocikat R, Steipe B, Thierfelder S. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J Immunol. 1995; 155:219-25; PMID:7602098
   PubMed Web of Science ®Google Scholar
• Ridgway JB, Presta LG, Carter P. ‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996; 9:617-21; PMID:8844834; http://dx.doi.org/10.1093/protein/9.7.617
   PubMedGoogle Scholar
• Gunasekaran K, Pentony M, Shen M, Garrett L, Forte C, Woodward A, Ng SB, Born T, Retter M, Manchulenko K, et al. Enhancing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG. J Biol Chem 2010; 285:19637-46; PMID:20400508; http://dx.doi.org/10.1074/jbc.M110.117382
   PubMed Web of Science ®Google Scholar
• Moore GL, Bautista C, Pong E, Nguyen DH, Jacinto J, Eivazi A, Muchhal US, Karki S, Chu SY, Lazar GA. A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens. Mabs 2011; 3:546-57; PMID:22123055; http://dx.doi.org/10.4161/mabs.3.6.18123
   PubMed Web of Science ®Google Scholar
• Kitazawa T, Igawa T, Sampei Z, Muto A, Kojima T, Soeda T, Yoshihashi K, Okuyama-Nishida Y, Saito H, Tsunoda H, et al. A bispecific antibody to factors IXa and × restores factor VIII hemostatic activity in a hemophilia A model. Nat Med. 2012; 18:1570-4; PMID:23023498; http://dx.doi.org/10.1038/nm.2942
   PubMed Web of Science ®Google Scholar
• Strop P, Ho WH, Boustany LM, Abdiche YN, Lindquist KC, Farias SE, Rickert M, Appah CT, Pascua E, Radcliffe T, et al. Generating bispecific human IgG1 and IgG2 antibodies from any antibody pair. J Mol Biol 2012; 420:204-19; PMID:22543237; http://dx.doi.org/10.1016/j.jmb.2012.04.020
   PubMed Web of Science ®Google Scholar
• Von Kreudenstein TS, Escobar-Carbrera E, Lario PI, D'Angelo I, Brault K, Kelly J, Durocher Y, Baardsnes J, Woods RJ, Xie MH, et al. Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design. Mabs 2013; 5:646-54; PMID:23924797; http://dx.doi.org/10.4161/mabs.25632
   PubMed Web of Science ®Google Scholar
• Klein C, Sustmann C, Thomas M, Stubenrauch K, Croasdale R, Schanzer J, Brinkmann U, Kettenberger H, Regula JT, Schaefer W. Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies. Mabs 2012; 4:653-63; PMID:22925968; http://dx.doi.org/10.4161/mabs.21379
   PubMed Web of Science ®Google Scholar
• Carter P. Bispecific human IgG by design. J Immunol Methods 2001; 248:7-15; PMID:11223065; http://dx.doi.org/10.1016/S0022-1759(00)00339-2
   PubMed Web of Science ®Google Scholar
• Jackman J, Chen Y, Huang A, Moffat B, Scheer JM, Leong SR, Lee WP, Zhang J, Sharma N, Lu Y, et al. Development of a two-part strategy to identify a therapeutic human bispecific antibody that inhibits IgE receptor signaling. J Biol Chem 2010; 285:20850-9; PMID:20444694; http://dx.doi.org/10.1074/jbc.M1-10.113910
   PubMed Web of Science ®Google Scholar
• Igawa T, Tsunoda H, Kikuchi Y, Yoshida M, Tanaka M, Koga A, Sekimori Y, Orita T, Aso Y, Hattori K, Tsuchiya M. VH/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody. Protein Eng Des Sel 2010; 23:667-77; PMID:20576629; http://dx.doi.org/10.1093/protein/gzq034
   PubMed Web of Science ®Google Scholar
• Liu Z, Leng EC, Gunasekaran K, Pentony M, Shen M, Howard M, Stoops J, Manchulenko K, Razinkov V, Liu H. et al. A novel antibody engineering strategy for making monovalent bispecific heterodimeric IgG antibodies by electrostatic steering mechanism. J Biol Chem 2015; 290:7535-62; PMID:25583986; http://dx.doi.org/10.1074/jbc.M114.620260
   PubMed Web of Science ®Google Scholar
• Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, et al. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat Biotechnol 2014; 32:191-8; PMID:24463572; http://dx.doi.org/10.1038/nbt.2797
   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; 108:11187-92; PMID:21690412; http://dx.doi.org/10.1073/pnas.1019002108
   PubMed Web of Science ®Google Scholar
• Kienast Y, Klein C, Scheuer W, Raemsch R, Lorenzon E, Bernicke D, Herting F, Yu S, The HH, Martarello L, et al. Ang-2-VEGF-A CrossMab, a novel bispecific human IgG1 antibody blocking VEGF-A and Ang-2 functions simultaneously, mediates potent antitumor, antiangiogenic, and antimetastatic efficacy. Clin Cancer Res 2013; 19:6730-40; PMID:24097868; http://dx.doi.org/10.1158/1078-0432.CCR-13-0081
   PubMed Web of Science ®Google Scholar
• Cheung GCM, Barathi VA, Tun BB, Yeo SW, Gan PP, Nyein CL, Regula J, Hartman G. Dual inhibition of angiopoietin-2 and vascular endothelial growth factor-A with Crossmab RG7716 suppressed laser-induced choroidal neovascularization in a non-human primate model. Invest Ophthalmol Vis Sci 2014; 55:1174; http://dx.doi.org/10.1167/iovs.13-11636
   Web of Science ®Google Scholar
• Lindhofer H, Mocikat R, Steipe B, Thierfelder S. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J Immunol 1995; 155:219-25; PMID:7602098
   PubMed Web of Science ®Google Scholar
• Suresh MR, Cuello AC, Milstein C. Bispecific monoclonal antibodies from hybrid hybridomas. Meth Enzymol 1986; 121:210-28; PMID:3724461; http://dx.doi.org/10.1016/0076-6879(86)21019-8
   PubMed Web of Science ®Google Scholar
• Smith W, Jarrett AL, Beattie RE, Corvalan JR. Immunoglobulins secreted by a hybrid-hybridoma: analysis of chain assemblies. Hybridoma 1992; 11:87-98; PMID:1737643; http://dx.doi.org/10.1089/hyb.1992.-11.87
   PubMed Web of Science ®Google Scholar
• Tada H, Toyoda Y, Iwasa S. Bispecific antibody-producing hybrid hybridoma and its use in one-step immunoassays for human lymphotoxin. Hybridoma. 1989; 8:73-83; PMID:2647617; http://dx.doi.org/10.1089/hyb.1989.8.73
   PubMed Web of Science ®Google Scholar
• Thomas M, Kienast Y, Scheuer W, Bähner M, Kaluza K, Gassner C, Herting F, Brinkmann U, Seeber S, Kavlie A, et al. A Novel Angiopoietin-2 Selective Fully Human Antibody with Potent Anti-Tumoral and Anti-Angiogenic Efficacy and Superior Side Effect Profile Compared to Pan-Angiopoietin-1/-2 Inhibitors. PLoS One 2013; 8:e54923; PMID:23405099; http://dx.doi.org/10.1371/journal.pone.0054923
   PubMed Web of Science ®Google Scholar
• Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997; 57:4593-9; PMID:9377574
   PubMed Web of Science ®Google Scholar
• In all cases, including Table and Figures, the intended bispecific antibody is underlined
   Google Scholar
• De Préval C, Fougereau M. Specific interaction between VH and VL regions of human monoclonal immunoglobulins. J Mol Biol. 1976; 102:657-78; http://dx.doi.org/10.1016/0022-2836(76)90340-5
   PubMed Web of Science ®Google Scholar
• Kranz DM, Voss EW Jr. Restricted reassociation of heavy and light chains from hapten-specific monoclonal antibodies. Proc Natl Acad Sci U S A 1981; 78:5807-11; PMID:6795637; http://dx.doi.org/10.1073/pnas.78.9.5807
   PubMed Web of Science ®Google Scholar
• Stevenson GT, Mole LE. The specificity of chain interactions among immunoglobulins. Combinations of gamma chains with kappa chains of the same subgroup as in the parent immunoglobulin G. Biochem J 1974; 139:369-74; PMID:4217181; http://dx.doi.org/10.1042/bj1390369
   PubMed Web of Science ®Google Scholar
• De Lau WB, Heije K, Neefjes JJ, Oosterwegel M, Rozemuller E, Bast BJ. Absence of preferential homologous H/L chain association in hybrid hybridomas. J Immunol 1991; 146:906-14; PMID:1899099
   PubMed Web of Science ®Google Scholar
• Hamel PA, Isenman DE, Klein MH, Luedtke R, Dorrington KJ. Structural basis for the preferential association of autologous immunoglobulin subunits: role of the J region of the light chain. Mol Immunol. 1984; 21:277-83; PMID:6427603; http://dx.doi.org/10.1016/0161-5890(84)90098-1
   PubMed Web of Science ®Google Scholar
• Hamel PA, Klein MH, Dorrington KJ. The role of the VL- and VH-segments in the preferential reassociation of immunoglobulin subunits. Mol Immunol 1986; 23:503-10; PMID:3092029; http://dx.doi.org/10.1016/0161-5890(86)90113-6
   PubMed Web of Science ®Google Scholar
• Hamel PA, Klein MH, Smith-Gill SJ, Dorrington KJ. Relative noncovalent association constant between immunoglobulin H and L chains is unrelated to their expression or antigen-binding activity. J Immunol 1987; 139:3012-20; PMID:3117886
   PubMed Web of Science ®Google Scholar
• Brezinschek HP, Foster SJ, Dörner T, Brezinschek RI, Lipsky PE. Pairing of variable heavy and variable kappa chains in individual naive and memory B cells. J Immunol 1998; 160:4762-7; PMID:9590222
   PubMed Web of Science ®Google Scholar
• Tiller T, Schuster I, Deppe D, Siegers K, Strohner R, Herrmann T, Berenguer M, Poujol D, Stehle J, Stark Y, et al. A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties. MAbs. 2013; 5:445-70; PMID:23571156; http://dx.doi.org/10.4161/mabs.24218
   PubMed Web of Science ®Google Scholar
• Jayaram N, Bhowmick P, Martin AC. Germline VH/VL pairing in antibodies. Protein Eng Des Sel 2012; 25:523-9; PMID:22802295; http://dx.doi.org/10.1093/protein/gzs043
   PubMed Web of Science ®Google Scholar