Fabs-in-tandem immunoglobulin is a novel and versatile bispecific design for engaging multiple therapeutic targets

References

• Park SS, Ryu CJ, Kang YJ, Kashmiri SV, Hong HJ. Generation and characterization of a novel tetravalent bispecific antibody that binds to hepatitis B virus surface antigens. Mol Immunol 2000; 37:1123-30; PMID:11451417; https://doi.org/10.1016/S0161-5890(01)00027-X
   PubMed Web of Science ®Google Scholar
• Fischer JA, Hueber AJ, Wilson S, Galm M, Baum W, Kitson C, Auer J, Lorenz SH, Moelleken J, Bader M, et al. Combined inhibition of tumor necrosis factor alpha and interleukin-17 as a therapeutic opportunity in rheumatoid arthritis: Development and characterization of a novel bispecific antibody. Arthritis Rheumatol 2015; 67:51-62; PMID:25303306; https://doi.org/10.1002/art.38896
   PubMed Web of Science ®Google Scholar
• Moores SL, Chiu ML, Bushey BS, Chevalier K, Luistro L, Dorn K, Brezski RJ, Haytko P, Kelly T, Wu SJ, et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res 2016; 76:3942-53; PMID:27216193; https://doi.org/10.1158/0008-5472.CAN-15-2833
   PubMed Web of Science ®Google Scholar
• Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res 2009; 69:4941-4; PMID:19509221; https://doi.org/10.1158/0008-5472.CAN-09-0547
   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 X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med 2012; 18:1570-4; PMID:23023498; https://doi.org/10.1038/nm.2942
   PubMed Web of Science ®Google Scholar
• Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008; 321:974-7; PMID:18703743; https://doi.org/10.1126/science.1158545
   PubMed Web of Science ®Google Scholar
• Sheridan C. Despite slow progress, bispecifics generate buzz. Nat Biotechnol 2016; 34:1215-7; PMID:27926715; https://doi.org/10.1038/nbt1216-1215
   PubMed Web of Science ®Google Scholar
• Brinkmann U, Kontermann RE. The making of bispecific antibodies. MAbs 2017; 9:182-212; PMID:28071970; https://doi.org/10.1080/19420862.2016.1268307
   PubMed Web of Science ®Google Scholar
• Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, Ellerman D, Shatz W, Reilly D, Yansura DG, et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat Biotechnol 2013; 31:753-8; PMID:23831709; https://doi.org/10.1038/nbt.2621
   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; https://doi.org/10.1073/pnas.1019002108
   PubMed Web of Science ®Google Scholar
• Wu C, Ying H, Grinnell C, Bryant S, Miller R, Clabbers A, Bose S, McCarthy D, Zhu RR, Santora L, et al. Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat Biotechnol 2007; 25:1290-7; PMID:17934452; https://doi.org/10.1038/nbt1345
   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; https://doi.org/10.1016/j.molimm.2015.01.003
   PubMed Web of Science ®Google Scholar
• Barrett A. Anti-IL-17 antibodies. International Publication Number: WO2007/070750A1 2006.
   Google Scholar
• Jesper P. Anti-human Interleukin-20 antibodies. International Publication Number: WO2010/000721 2009.
   Google Scholar
• Burmester GR, Feist E, Dörner T. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol 2014; 10:77-88; PMID:24217582; https://doi.org/10.1038/nrrheum.2013.168
   PubMed Web of Science ®Google Scholar
• Guo A, Villén J, Kornhauser J, Lee KA, Stokes MP, Rikova K, Possemato A, Nardone J, Innocenti G, Wetzel R, et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc Natl Acad Sci U S A 2008; 105:692-7; PMID:18180459; https://doi.org/10.1073/pnas.0707270105
   PubMed Web of Science ®Google Scholar
• Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D, Lifshits E, Toschi L, Rogers A, Mok T, Sequist L, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010; 17:77-88; PMID:20129249; https://doi.org/10.1016/j.ccr.2009.11.022
   PubMed Web of Science ®Google Scholar
• Jakobovits A. Human monoclonal antibodies to epidermal growth factor receptor. 1997; Patent No.: US6235883.
   Google Scholar
• Michaud NR. Antibodies to cMet. 2004; Patent No.: US7498420.
   Google Scholar
• Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005; 2:0225-35; PMID:15737014; https://dx.doi/10.1371/journal.pmed.0020073
   PubMed Web of Science ®Google Scholar
• Kwak EL, Sordella R, Bell DW, Godin-Heymann N, Okimoto RA, Brannigan BW, Harris PL, Driscoll DR, Fidias P, Lynch TJ, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci U S A 2005; 102:7665-70; PMID:15897464; https://doi.org/10.1073/pnas.0502860102
   PubMed Web of Science ®Google Scholar
• Fan G, Wang Z, Hao M, Li J. Bispecific antibodies and their applications. J Hematol Oncol 2015; 8:130; PMID:26692321; https://doi.org/10.1186/s13045-015-0227-0
   PubMed Web of Science ®Google Scholar
• Piccione EC, Juarez S, Liu J, Tseng S, Ryan CE, Narayanan C, Wang L, Weiskopf K, Majeti R. A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells. MAbs 2015; 7:946-56; PMID:26083076; https://doi.org/10.1080/19420862.2015.1062192
   PubMed Web of Science ®Google Scholar
• Nagorsen D, Bargou R, Ruttinger D, Kufer P, Baeuerle PA, Zugmaier G. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma 2009; 50:886-91; PMID:19455460; https://doi.org/10.1080/10428190902943077
   PubMed Web of Science ®Google Scholar
• Wec AZ, Nyakatura EK, Herbert AS, Howell KA, Holtsberg FW, Bakken RR, Mittler E, Christin JR, Shulenin S, Jangra RK, et al. A “Trojan horse” bispecific-antibody strategy for broad protection against ebolaviruses. Science 2016; 354:350-4; PMID:27608667; https://doi.org/10.1126/science.aag3267
   PubMed Web of Science ®Google Scholar
• Bournazos S, Gazumyan A, Seaman MS, Nussenzweig MC, Ravetch J V. Bispecific Anti-HIV-1 antibodies with enhanced breadth and potency. Cell 2016; 165:1609-20; PMID:27315478; https://doi.org/10.1016/j.cell.2016.04.050
   PubMed Web of Science ®Google Scholar
• Wu X, Sereno AJ, Huang F, Lewis SM, Lieu RL, Weldon C, Torres C, Fine C, Batt MA, Jonathan R, et al. Fab-based bispecific antibody formats with robust biophysical properties and biological activity. MAbs 2015; 862:470-82; PMID:25774965; https://doi.org/10.1080/19420862.2015.1022694
   PubMed Web of Science ®Google Scholar
• Golay J, Choblet S, Iwaszkiewicz J, Cérutti P, Ozil A, Loisel S, Pugnière M, Ubiali G, Zoete V, Michielin O, et al. Design and validation of a novel generic platform for the production of tetravalent IgG1-like bispecific antibodies. J Immunol 2016; 196:3199-211; PMID:26921308; https://doi.org/10.4049/jimmunol.1501592
   PubMed Web of Science ®Google Scholar
• Le Gall F, Reusch U, Little M, Kipriyanov SM. Effect of linker sequences between the antibody variable domains on the formation, stability and biological activity of a bispecific tandem diabody. Protein Eng Des Sel 2004; 17:357-66; PMID:15126676; https://doi.org/10.1093/protein/gzh039
   PubMed Web of Science ®Google Scholar
• Davé E, Adams R, Zaccheo O, Carrington B, Compson JE, Dugdale S, Airey M, Malcolm S, Hailu H, Wild G, et al. Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding. MAbs 2016; 8:1319-35; PMID:27532598; https://doi.org/10.1080/19420862.2016.1210747
   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; https://doi.org/10.1038/nbt.2797
   PubMed Web of Science ®Google Scholar
• Wu C, Ying H, Bose S, Miller R, Medina L, Santora L, Ghayur T. Molecular construction and optimization of anti-human IL-1α/β dual variable domain immunoglobulin (DVD-Ig) molecules. MAbs 2009; 1:339-47; PMID:20068402; https://doi.org/10.4161/mabs.1.4.8755
   PubMed Web of Science ®Google Scholar
• Fenn S, Schiller CB, Griese JJ, Duerr H, Imhof-Jung S, Gassner C, Moelleken J, Regula JT, Schaefer W, Thomas M, et al. Crystal structure of an Anti-Ang2 crossfab demonstrates complete structural and functional integrity of the variable domain. PLoS One 2013; 8:1-7; PMID:23613981; https://doi.org/10.1371/journal.pone.0061953
   PubMed Web of Science ®Google Scholar
• Castoldi R, Ecker V, Wiehle L, Majety M, Busl-Schuller R, Asmussen M, Nopora A, Jucknischke U, Osl F, Kobold S, et al. A novel bispecific EGFR/Met antibody blocks tumor-promoting phenotypic effects induced by resistance to EGFR inhibition and has potent antitumor activity. Oncogene 2013; 32:5593-601; PMID:23812422; https://doi.org/10.1038/onc.2013.245
   PubMed Web of Science ®Google Scholar
• Parton RG, Schrotz P, Bucci C, Gruenberg J. Plasticity of early endosomes. J Cell Sci 1992; 103(Pt 2):335-48; PMID:1478937
   PubMed Web of Science ®Google Scholar
• St. Pierre CA, Leonard D, Corvera S, Kurt-Jones EA, Finberg RW. Antibodies to cell surface proteins redirect intracellular trafficking pathways. Exp Mol Pathol 2011; 91:723-32; PMID:21819978; https://doi.org/10.1016/j.yexmp.2011.05.011
   PubMed Web of Science ®Google Scholar
• Weflen AW, Baier N, Tang Q-J, Van den Hof M, Blumberg RS, Lencer WI, Massol RH. Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules. Mol Biol Cell 2013; 24:2398-405; PMID:23741050; https://doi.org/10.1091/mbc.E13-04-0174
   PubMed Web of Science ®Google Scholar
• Wang Q, Villeneuve G, Wang Z. Control of epidermal growth factor receptor endocytosis by receptor dimerization, rather than receptor kinase activation. EMBO Rep 2005; 6:942-8; PMID:16113650; https://doi.org/10.1038/sj.embor.7400491
   PubMed Web of Science ®Google Scholar
• Klein C, Schaefer W, Regula JT. The use of CrossMAb technology for the generation of bi- and multispecific antibodies. MAbs 2016; 8:1010-20; PMID:27285945; https://doi.org/10.1080/19420862.2016.1197457
   PubMed Web of Science ®Google Scholar
• Schuurman J, Parren PWHI. Editorial overview: Special section: New concepts in antibody therapeutics: What's in store for antibody therapy? Curr Opin Immunol 2016; 40:vii-xiii; PMID:27083411; https://doi.org/10.1016/j.coi.2016.04.001
   PubMed Web of Science ®Google Scholar
• Sheridan C. Amgen's bispecific antibody puffs across finish line. Nat Biotechnol 2015; 33:219-21; PMID:25748895; https://doi.org/10.1038/nbt0315-219
   PubMed Web of Science ®Google Scholar
• Zlabinger GJ, Stuhlmeier KM, Eher R, Schmaldienst S, Klauser R, Vychytil A, Watschinger B, Traindl O, Kovarik J, Pohanka E. Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal antibody treatment. J Clin Immunol 1992; 12:170-7; PMID:1400897; https://doi.org/10.1007/BF00918085
   PubMed Web of Science ®Google Scholar
• Ferran C, Sheehan K, Dy M, Schreiber R, Merite S, Landais P, Noel LH, Grau G, Bluestone J, Bach JF, et al. Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: Further evidence for transient in vivo T cell activation. Eur J Immunol 1990; 20:509-15; PMID:2138557; https://doi.org/10.1002/eji.1830200308
   PubMed Web of Science ®Google Scholar
• Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 2010; 9:325-38; PMID:20305665; https://doi.org/10.1038/nrd3003
   PubMed Web of Science ®Google Scholar