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Review Article

Single-domain antibodies for biomedical applications

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Pages 21-28 | Received 20 May 2015, Accepted 24 Sep 2015, Published online: 09 Nov 2015

References

  • Aggarwal SR. What's fueling the biotech engine – 2010 to 2011. Nat Biotechnol 2011;29:1083–1089
  • Aggarwal SR. What's fueling the biotech engine – 2011 to 2012. Nat Biotechnol 2012;30:1191–1197
  • Buss NA, Henderson SJ, McFarlane M, et al. Monoclonal antibody therapeutics: history and future. Curr Opin Pharmacol 2012;12:615–622
  • Reichert JM. Marketed therapeutic antibodies compendium. MAbs 2012;4:413–415
  • Reichert JM. Which are the antibodies to watch in 2013? MAbs 2013;5:1–4
  • Dübel S. Recombinant therapeutic antibodies. Appl Microbiol Biotechnol 2007;74:723–729
  • Reichert JM. Antibodies to watch in 2015. MAbs 2015;7:1–8
  • Mordenti J, Cuthbertson RA, Ferrara N, et al. Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol 1999;27:536–544
  • Vaneycken I, D'Huyvetter M, Hernot S, et al. Immuno-imaging using nanobodies. Curr Opin Biotechnol 2011;22:877–881
  • Huang L, Gainkam LO, Caveliers V, et al. SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression. Mol Imaging Biol 2008;10:167–175
  • Kenanova V, Wu AM. Tailoring antibodies for radionuclide delivery. Expert Opin Drug Deliv 2006;3:53–70
  • Van de Wiele C, Revets H, Mertens N. Radioimmunoimaging. Advances and prospects. Q J Nucl Med Mol Imaging 2004;48:317–325
  • Casi G, Neri D. Antibody-drug conjugates: basic concepts, examples and future perspectives. J Control Release 2012;161:422–428
  • Bouchard H, Viskov C, Garcia-Echeverria C. Antibody-drug conjugates - a new wave of cancer drugs. Bioorg Med Chem Lett 2014;24:5357–5363
  • Pasche N, Neri D. Immunocytokines: a novel class of potent armed antibodies. Drug Discov Today 2012;17:583–590
  • Huehls AM, Coupet TA, Sentman CL. Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol 2014;93:290–296
  • Kolmar H. Natural and engineered cystine knot miniproteins for diagnostic and therapeutic applications. Curr Pharm Des 2011;17:4329–4336
  • Richter A, Eggenstein E, Skerra A. Anticalins: exploiting a non-Ig scaffold with hypervariable loops for the engineering of binding proteins. FEBS Lett 2014;588:213–218
  • Boersma YL, Plückthun A. DARPins and other repeat protein scaffolds: advances in engineering and applications. Curr Opin Biotechnol 2011;22:849–857
  • Ying T, Gong R, Ju TW, et al. Engineered Fc based antibody domains and fragments as novel scaffolds. Biochim Biophys Acta 2014;1844:1977–1982
  • Wozniak-Knopp G, Bartl S, Bauer A, et al. Introducing antigen-binding sites in structural loops of immunoglobulin constant domains: Fc fragments with engineered HER2/neu-binding sites and antibody properties. Protein Eng Des Sel 2010;23:289–297
  • Hamers-Casterman C, Atarhouch T, Muyldermans S, et al. Naturally occurring antibodies devoid of light chains. Nature 1993;363:446–448
  • Greenberg AS, Avila D, Hughes M, et al. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. Nature 1995;374:168–173
  • Davies J, Riechmann L. Single antibody domains as small recognition units: design and in vitro antigen selection of camelized, human VH domains with improved protein stability. Protein Eng 1996;9:531–537
  • Holt LJ, Herring C, Jespers LS, et al. Domain antibodies: proteins for therapy. Trends Biotechnol. 2003;21:484–490
  • Dimitrov DS. Engineered CH2 domains (nanoantibodies). MAbs 2009;1:26–28
  • van der Linden RH, Frenken LG, de Geus B, et al. Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies. Biochim Biophys Acta 1999;1431:37–46
  • Wesolowski J, Alzogaray V, Reyelt J, et al. Single domain antibodies: promising experimental and therapeutic tools in infection and immunity. Med Microbiol Immunol 2009;198:157–174
  • Conrath K, Vincke C, Stijlemans B, et al. Antigen binding and solubility effects upon the veneering of a camel VHH in framework-2 to mimic a VH. J Mol Biol 2005;350:112–125
  • Zarschler K, Witecy S, Kapplusch F, et al. High-yield production of functional soluble single-domain antibodies in the cytoplasm of Escherichia coli. Microb Cell Fact 2013;12:97
  • Li F, Vijayasankaran N, Shen AY, et al. Cell culture processes for monoclonal antibody production. MAbs 2010;2:466–479
  • Arbabi Ghahroudi M, Desmyter A, Wyns L, et al. Selection and identification of single domain antibody fragments from camel heavy-chain antibodies. FEBS Lett 1997;414:521–526
  • Ryckaert S, Pardon E, Steyaert J, Callewaert N. Isolation of antigen-binding camelid heavy chain antibody fragments (nanobodies) from an immune library displayed on the surface of Pichia pastoris. J Biotechnol 2010;145:93–98
  • Yau KY, Groves MA, Li S, et al. Selection of hapten-specific single-domain antibodies from a non-immunized llama ribosome display library. J Immunol Methods 2003;281:161–175
  • Fleetwood F, Devoogdt N, Pellis M, et al. Surface display of a single-domain antibody library on Gram-positive bacteria. Cell Mol Life Sci 2013;70:1081–1093
  • Monegal A, Ami D, Martinelli C, et al. Immunological applications of single-domain llama recombinant antibodies isolated from a naïve library. Protein Eng Des Sel 2009;22:273–280
  • Goldman ER, Anderson GP, Liu JL, et al. Facile generation of heat-stable antiviral and antitoxin single domain antibodies from a semisynthetic llama library. Anal Chem. 2006;78:8245–8255
  • Vincke C, Loris R, Saerens D, et al. General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold. J Biol Chem 2009;284:3273–3284
  • Callewaert F, Roodt J, Ulrichts H, et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood 2012;120:3603–3610
  • Kratz F, Elsadek B. Clinical impact of serum proteins on drug delivery. J Control Release 2012;161:429–445
  • Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006;5:993–996
  • Jahnichen S, Blanchetot C, Maussang D, et al. CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc Natl Acad Sci USA 2010;107:20565–20570
  • Maussang D, Mujic-Delic A, Descamps FJ, et al. Llama-derived single variable domains (nanobodies) directed against chemokine receptor CXCR7 reduce head and neck cancer cell growth in vivo. J Biol Chem 2013;288:29562–29572
  • Habib I, Smolarek D, Hattab C, et al. V(H)H (nanobody) directed against human glycophorin A: a tool for autologous red cell agglutination assays. Anal Biochem 2013;438:82–89
  • Zhu M, Gong X, Hu Y, et al. Streptavidin-biotin-based directional double Nanobody sandwich ELISA for clinical rapid and sensitive detection of influenza H5N1. J Transl Med 2014;12:352
  • Movahedi K, Schoonooghe S, Laoui D, et al. Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages. Cancer Res 2012;72:4165–4177
  • Zielonka S, Empting M, Grzeschik J, et al. Structural insights and biomedical potential of IgNAR scaffolds from sharks. MAbs 2015;7:15–25
  • Barelle C, Gill DS, Charlton K. Shark novel antigen receptors-the next generation of biologic therapeutics? Adv Exp Med Biol 2009;655:49–62
  • Stanfield RL, Dooley H, Flajnik MF, Wilson IA. Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science 2004;305:1770–1773
  • Dooley H, Stanfield RL, Brady RA, Flajnik MF. First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate. Proc Natl Acad Sci USA 2006;103:1846–1851
  • Zielonka S, Könning D, Grzeschik J, et al. The shark strikes twice: hypervariable loop 2 of shark IgNAR antibody variable domains and its potential to function as an autonomous paratope. Mar Biotechnol (NY) 2015;17:386–392
  • Diaz M, Stanfield RL, Greenberg AS, Flajnik MF. Structural analysis, selection, and ontogeny of the shark new antigen receptor (IgNAR): identification of a new locus preferentially expressed in early development. Immunogenetics 2002;54:501–512
  • Kovalenko OV, Olland A, Piche-Nicholas N, et al. Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis. J Biol Chem 2013;288:17408–17419
  • Stanfield RL, Dooley H, Verdino P, et al. Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding. J Mol Biol 2007;367:358–372
  • Streltsov VA, Carmichael JA, Nuttall SD. Structure of a shark IgNAR antibody variable domain and modeling of an early-developmental isotype. Protein Sci 2005;14:2901–2909
  • Simmons DP, Streltsov VA, Dolezal O, et al. Shark IgNAR antibody mimotopes target a murine immunoglobulin through extended CDR3 loop structures. Proteins 2008;71:119–130
  • Flajnik MF, Deschacht N, Muyldermans S. A case of convergence: why did a simple alternative to canonical antibodies arise in sharks and camels? PLoS Biol 2011;9:e1001120
  • Streltsov VA, Varghese JN, Carmichael JA, et al. Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor. Proc Natl Acad Sci USA 2004;101:12444–12449
  • Henderson KA, Streltsov VA, Coley AM, et al. Structure of an IgNAR-AMA1 complex: targeting a conserved hydrophobic cleft broadens malarial strain recognition. Structure 2007;15:1452–1466
  • Feige MJ, Gräwert MA, Marcinowski M, et al. The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins. Proc Natl Acad Sci USA 2014;111:8155–8160
  • Liu JL, Anderson GP, Delehanty JB, et al. Selection of cholera toxin specific IgNAR single-domain antibodies from a naïve shark library. Mol Immunol 2007;44:1775–1783
  • Goodchild SA, Dooley H, Schoepp RJ, et al. Isolation and characterisation of Ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries. Mol Immunol 2011;48:2027–2037
  • Zielonka S, Weber N, Becker S, et al. Shark attack: high affinity binding proteins derived from shark vNAR domains by stepwise in vitro affinity maturation. J Biotechnol 2014;191:236–245
  • Kovaleva M, Ferguson L, Steven J, et al. Shark variable new antigen receptor biologics – a novel technology platform for therapeutic drug development. Expert Opin Biol Ther 2014;14:1527–1539
  • Muller MR, Saunders K, Grace C, et al. Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain. MAbs 2012;4:673–685
  • Simmons DP, Abregu FA, Krishnan UV, et al. Dimerisation strategies for shark IgNAR single domain antibody fragments. J Immunol Methods 2006;315:171–184
  • Uth C, Zielonka S, Hörner S, et al. A chemoenzymatic approach to protein immobilization onto crystalline cellulose nanoscaffolds. Angew Chem Int Ed Engl 2014;53:12618–12623
  • Streltsov VA, Varghese JN, Masters CL, Nuttall SD. Crystal structure of the amyloid-β p3 fragment provides a model for oligomer formation in Alzheimer's disease. J Neurosci 2011;31:1419–1426
  • Walsh R, Nuttall S, Revill P, et al. Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody. Virology 2011;411:132–141
  • Liu JL, Anderson GP, Goldman ER. Isolation of anti-toxin single domain antibodies from a semi-synthetic spiny dogfish shark display library. BMC Biotechnol 2007;7:78
  • Nuttall SD, Humberstone KS, Krishnan UV, et al. Selection and affinity maturation of IgNAR variable domains targeting Plasmodium falciparum AMA1. Proteins 2004;55:187–197
  • Nuttall SD, Krishnan UV, Doughty L, et al. Isolation and characterization of an IgNAR variable domain specific for the human mitochondrial translocase receptor Tom70. Eur J Biochem 2003;270:3543–3554
  • Ohtani M, Hikima J, Jung TS, et al. Variable domain antibodies specific for viral hemorrhagic septicemia virus (VHSV) selected from a randomized IgNAR phage display library. Fish Shellfish Immunol 2013;34:724–728
  • Bojalil R, Mata-Gonzalez MT, Sanchez-Munoz F, et al. Anti-tumor necrosis factor VNAR single domains reduce lethality and regulate underlying inflammatory response in a murine model of endotoxic shock. BMC Immunol 2013;14:17
  • Kopsidas G, Roberts AS, Coia G, et al. In vitro improvement of a shark IgNAR antibody by Qbeta replicase mutation and ribosome display mimics in vivo affinity maturation. Immunol Lett 2006;107:163–168
  • Holz JB. The TITAN trial – assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci 2012;46:343–346
  • Dooley H, Flajnik MF, Porter AJ. Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display. Mol Immunol 2003;40:25–33
  • Siontorou CG. Nanobodies as novel agents for disease diagnosis and therapy. Int J Nanomedicine 2013;8:4215–4227
  • Vaneycken I, Govaert J, Vincke C, et al. In vitro analysis and in vivo tumor targeting of a humanized, grafted nanobody in mice using pinhole SPECT/micro-CT. J Nucl Med 2010;51:1099–1106
  • Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs 2010;2:256–265
  • Getts DR, Getts MT, McCarthy DP, et al. Have we overestimated the benefit of human(ized) antibodies? MAbs 2010;2:682–694
  • Radstake TR, Svenson M, Eijsbouts AM, et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis 2009;68:1739–1745
  • Bender NK, Heilig CE, Droll B, et al. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int 2007;27:269–274
  • West RL, Zelinkova Z, Wolbink GJ, et al. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease. Aliment Pharmacol Ther 2008;28:1122–1126
  • Kim DY, To R, Kandalaft H, et al. Antibody light chain variable domains and their biophysically improved versions for human immunotherapy. MAbs 2014;6:219–235
  • Ewert S, Huber T, Honegger A, Plückthun A. Biophysical properties of human antibody variable domains. J Mol Biol 2003;325:531–553
  • Martin F, Volpari C, Steinkuhler C, et al. Affinity selection of a camelized V(H) domain antibody inhibitor of hepatitis C virus NS3 protease. Protein Eng 1997;10:607–614
  • Jespers L, Schon O, Famm K, Winter G. Aggregation-resistant domain antibodies selected on phage by heat denaturation. Nature Biotechnol 2004;22:1161–1165
  • To R, Hirama T, Arbabi-Ghahroudi M, et al. Isolation of monomeric human V(H)s by a phage selection. J Biol Chem 2005;280:41395–41403
  • Hussack G, Keklikian A, Alsughayyir J, et al. A V(L) single-domain antibody library shows a high-propensity to yield non-aggregating binders. PEDS 2012;25:313–318
  • Söderlind E, Vergeles M, Borrebaeck CA. Domain libraries: synthetic diversity for de novo design of antibody V-regions. Gene 1995;160:269–272
  • van den Beucken T, van Neer N, Sablon E, et al. Building novel binding ligands to B7.1 and B7.2 based on human antibody single variable light chain domains. J Mol Biol 2001;310:591–601
  • Paz K, Brennan LA, Iacolina M, et al. Human single-domain neutralizing intrabodies directed against Etk kinase: a novel approach to impair cellular transformation. Molec Cancer Ther 2005;4:1801–1809
  • Arbabi-Ghahroudi M, Tanha J, MacKenzie R. Isolation of monoclonal antibody fragments from phage display libraries. Methods Mol Biol 2009;502:341–364
  • Arbabi-Ghahroudi M, Mackenzie R, Tanha J. Site-directed mutagenesis for improving biophysical properties of VH domains. Methods Mol Biol 2010;634:309–330
  • Kim DY, Hussack G, Kandalaft H, Tanha J. Mutational approaches to improve the biophysical properties of human single-domain antibodies. Biochim Biophys Acta 2014;1844:1983–2001
  • Famm K, Hansen L, Christ D, Winter G. Thermodynamically stable aggregation-resistant antibody domains through directed evolution. J Mol Biol 2008;376:926–931
  • Holliger P, Hudson PJ. Engineered antibody fragments and the rise of single domains. Nature Biotechnol 2005;23:1126–1136
  • Holland MC, Wurthner JU, Morley PJ, et al. Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-alpha receptor 1. J Clin Immunol 2013;33:1192–1203
  • O'Connor-Semmes RL, Lin J, Hodge RJ, et al. GSK2374697, a novel albumin-binding domain antibody (AlbudAb), extends systemic exposure of exendin-4: first study in humans–PK/PD and safety. Clin Pharmacol Therap 2014;96:704–712
  • Holt LJ, Basran A, Jones K, et al. Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs. PEDS 2008;21:283–288
  • Gay RD, Clarke AW, Elgundi Z, et al. Anti-TNFα domain antibody construct CEP-37247: full antibody functionality at half the size. MAbs 2010;2:625–638
  • Chen W, Feng Y, Prabakaran P, et al. Exceptionally potent and broadly cross-reactive, bispecific multivalent HIV-1 inhibitors based on single human CD4 and antibody domains. J Virol 2014;88:1125–1139
  • Feng M, Gao W, Wang R, et al. Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma. Proc Natl Acad Sci USA 2013;110:E1083–E1091
  • Chen W, Feng Y, Zhao Q, et al. Human monoclonal antibodies targeting nonoverlapping epitopes on insulin-like growth factor II as a novel type of candidate cancer therapeutics. Molec Cancer Therap 2012;11:1400–1410
  • Tang Z, Feng M, Gao W, et al. A human single-domain antibody elicits potent antitumor activity by targeting an epitope in mesothelin close to the cancer cell surface. Molec Cancer Therap 2013;12:416–426
  • Miao Q, Shang B, Ouyang Z, et al. Generation and antitumor effects of an engineered and energized fusion protein VL-LDP-AE composed of single-domain antibody and lidamycin. Sci China C Life Sci 2007;50:447–456
  • Suchard SJ, Davis PM, Kansal S, et al. A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety. J. Immunol 2013;191:4599–4610
  • Gong R, Wang Y, Ying T, Dimitrov DS. Bispecific engineered antibody domains (nanoantibodies) that interact noncompetitively with an HIV-1 neutralizing epitope and FcRn. PLoS One 2012;7:e42288
  • Chen W, Gong R, Ying T, et al. Discovery of novel candidate therapeutics and diagnostics based on engineered human antibody domains. Curr Drug Discov Technol 2014;11:28–40
  • Xiao X, Feng Y, Vu BK, et al. A large library based on a novel (CH2) scaffold: identification of HIV-1 inhibitors. Biochem Biophys Res Commun 2009;387:387–392
  • Gong R, Wang Y, Feng Y, et al. Shortened engineered human antibody CH2 domains: increased stability and binding to the human neonatal Fc receptor. J Biol Chem 2011;286:27288–27293
  • Gehlsen K, Gong R, Bramhill D, et al. Pharmacokinetics of engineered human monomeric and dimeric CH2 domains. MAbs 2012;4:466–474
  • Ying T, Chen W, Feng Y, et al. Engineered soluble monomeric IgG1 CH3 domain: generation, mechanisms of function, and implications for design of biological therapeutics. J Biol Chem 2013;288:25154–25164

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