Advertisement

pp 1-32 | Cite as

Therapeutic Antibody Engineering and Selection Strategies

  • Joana Ministro
  • Ana Margarida Manuel
  • Joao GoncalvesEmail author
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series

Abstract

Antibody drugs became an increasingly important element of the therapeutic landscape. Their accomplishment has been driven by many unique properties, in particular by their very high specificity and selectivity, in contrast to the off-target liabilities of small molecules (SMs). Antibodies can bring additional functionality to the table with their ability to interact with the immune system, and this can be further manipulated with advances in antibody engineering.

The expansion of strategies related to discovery technologies of monoclonal antibodies (mAbs) (phage display, yeast display, ribosome display, bacterial display, mammalian cell surface display, mRNA display, DNA display, transgenic animal, and human B cell derived) opened perspectives for the screening and the selection of therapeutic antibodies for, theoretically, any target from any kind of organism. Moreover, antibody engineering technologies were developed and explored to obtain chosen characteristics of selected leading candidates such as high affinity, low immunogenicity, improved functionality, improved protein production, improved stability, and others. This chapter contains an overview of discovery technologies, mainly display methods and antibody humanization methods for the selection of therapeutic humanized and human mAbs that appeared along the development of these technologies and thereafter. The increasing applications of these technologies will be highlighted in the antibody engineering area (affinity maturation, guided selection to obtain human antibodies) giving promising perspectives for the development of future therapeutics.

Graphical Abstract

Keywords

Anti-drug antibodies Biosimilars European market Immunogenicity Product information Recombinant drugs Summary of product characteristics Therapeutic biologics 

References

  1. 1.
    Riedel S (2005) Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent) 18:21–25.  https://doi.org/10.1080/08998280.2005.11928028CrossRefGoogle Scholar
  2. 2.
    von Behring E, Kitasato S (1991) The mechanism of diphtheria immunity and tetanus immunity in animals. Mol Immunol 28:1317, 1319–1320Google Scholar
  3. 3.
    Davies DR, Chacko S (1993) Antibody structure. Acc Chem Res 26:421–427.  https://doi.org/10.1021/ar00032a005CrossRefGoogle Scholar
  4. 4.
    Pauling L (1940) A theory of the structure and process of formation of antibodies. J Am Chem Soc 62:2643–2657.  https://doi.org/10.1021/ja01867a018CrossRefGoogle Scholar
  5. 5.
    Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497Google Scholar
  6. 6.
    Hooks MA, Wade CS, Millikan WJ (1991) Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. Pharmacotherapy 11:26–37Google Scholar
  7. 7.
    Singh S, Kumar NK, Dwiwedi P et al (2018) Monoclonal antibodies: a review. Curr Clin Pharmacol 13:85–99.  https://doi.org/10.2174/1574884712666170809124728CrossRefGoogle Scholar
  8. 8.
    Strohl WR (2017) Analysis of the current antibody landscape. In: Antibody engineering and therapeutics. San DiegoGoogle Scholar
  9. 9.
    Goldsby RA, Kindt TJ, Osborne BA, Kuby J (2003) Immunology, 5th edn. W. H. Freeman, New YorkGoogle Scholar
  10. 10.
    Poljak RJ, Amzel LM, Avey HP et al (1973) Three-dimensional structure of the Fab’ fragment of a human immunoglobulin at 2.8-A resolution. Proc Natl Acad Sci 70:3305–3310.  https://doi.org/10.1073/pnas.70.12.3305CrossRefGoogle Scholar
  11. 11.
    Inbar D, Hochman J, Givol D (1972) Localization of antibody-combining sites within the variable portions of heavy and light chains. Proc Natl Acad Sci 69:2659–2662.  https://doi.org/10.1073/pnas.69.9.2659CrossRefGoogle Scholar
  12. 12.
    Presta LG (2006) Engineering of therapeutic antibodies to minimize immunogenicity and optimize function. Adv Drug Deliv Rev 58:640–656.  https://doi.org/10.1016/j.addr.2006.01.026CrossRefGoogle Scholar
  13. 13.
    García Merino A (2011) Monoclonal antibodies. Basic features. Neurologia 26:301–306.  https://doi.org/10.1016/j.nrl.2010.10.005CrossRefGoogle Scholar
  14. 14.
    Cruse JM, Lewis R (2010) Atlas of immunology, 3rd edn. CRC Press, Boca RatonGoogle Scholar
  15. 15.
    Male D, Brostoff J, Roth D, Roitt I (2006) Immunology, 7th edn. Elsevier, PhiladelphiaGoogle Scholar
  16. 16.
    Vandyk L, Meek K (1992) Assembly of IgH CDR3: mechanism, regulation, and influence on antibody diversity. Int Rev Immunol 8:123–133.  https://doi.org/10.3109/08830189209055568CrossRefGoogle Scholar
  17. 17.
    Morea V, Lesk AM, Tramontano A (2000) Antibody modeling: implications for engineering and design. Methods 20:267–279.  https://doi.org/10.1006/meth.1999.0921CrossRefGoogle Scholar
  18. 18.
    Padlan EA, Abergel C, Tipper JP (1995) Identification of specificity-determining residues in antibodies. FASEB J 9:133–139.  https://doi.org/10.1096/fasebj.9.1.7821752CrossRefGoogle Scholar
  19. 19.
    Mandigan M, Martinko J (2006) Brock biology of microorganisms, 11th edn. Pearson Prentice Hall, Upper Saddle RiverGoogle Scholar
  20. 20.
    O’Kennedy R, Fitzgerald S, Murphy C (2017) Don’t blame it all on antibodies – the need for exhaustive characterisation, appropriate handling, and addressing the issues that affect specificity. TrAC Trends Anal Chem 89:53–59.  https://doi.org/10.1016/j.trac.2017.01.009CrossRefGoogle Scholar
  21. 21.
    Murphy K (2012) Janeway’s immunobiology, 8th edn. Garland Science, New YorkGoogle Scholar
  22. 22.
    Hozumi N, Tonegawa S (1976) Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci 73:3628–3632.  https://doi.org/10.1073/pnas.73.10.3628CrossRefGoogle Scholar
  23. 23.
    Goodnow CC, Basten A (1989) Self-tolerance in B lymphocytes. Semin Immunol 1:125–135Google Scholar
  24. 24.
    Janeway C, Travers JP, Walport M, Shlomchik M (2001) Immunobiology: the immune system in health and disease, 5th edn. Garland Science, New YorkGoogle Scholar
  25. 25.
    Chan TD, Gatto D, Wood K et al (2009) Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J Immunol 183:3139–3149.  https://doi.org/10.4049/jimmunol.0901690CrossRefGoogle Scholar
  26. 26.
    Parra D, Takizawa F, Sunyer JO (2013) Evolution of B cell immunity. Annu Rev Anim Biosci 1:65–97.  https://doi.org/10.1146/annurev-animal-031412-103651CrossRefGoogle Scholar
  27. 27.
    Goodnow CC, Vinuesa CG, Randall KL et al (2010) Control systems and decision making for antibody production. Nat Immunol 11:681–688.  https://doi.org/10.1038/ni.1900CrossRefGoogle Scholar
  28. 28.
    Tonegawa S (1983) Somatic generation of antibody diversity. Nature 302:575–581.  https://doi.org/10.1038/302575a0CrossRefGoogle Scholar
  29. 29.
    Oettinger M, Schatz D, Gorka C, Baltimore D (1990) RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523.  https://doi.org/10.1126/science.2360047CrossRefGoogle Scholar
  30. 30.
    Bassing CH, Alt FW, Hughes MM et al (2000) Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule. Nature 405:583–586.  https://doi.org/10.1038/35014635CrossRefGoogle Scholar
  31. 31.
    Mansilla-Soto J, Cortes P (2003) VDJ recombination: artemis and its in vivo role in hairpin opening. J Exp Med 197:543–547.  https://doi.org/10.1084/jem.20022210CrossRefGoogle Scholar
  32. 32.
    Mak TW, Saunders ME (2006) The immunoglobulin genes. In: The immune response. Elsevier, Amsterdam, pp 179–208Google Scholar
  33. 33.
    Motea EA, Berdis AJ (2010) Terminal deoxynucleotidyl transferase: the story of a misguided DNA polymerase. Biochim Biophys Acta – Proteins Proteomics 1804:1151–1166.  https://doi.org/10.1016/j.bbapap.2009.06.030CrossRefGoogle Scholar
  34. 34.
    Malu S, Malshetty V, Francis D, Cortes P (2012) Role of non-homologous end joining in V(D)J recombination. Immunol Res 54:233–246.  https://doi.org/10.1007/s12026-012-8329-zCrossRefGoogle Scholar
  35. 35.
    Helmink BA, Sleckman BP (2012) The response to and repair of RAG-mediated DNA double-strand breaks. Annu Rev Immunol 30:175–202.  https://doi.org/10.1146/annurev-immunol-030409-101320CrossRefGoogle Scholar
  36. 36.
    Chu H (2013) VDJ recombination. Cell 94:411–414.  https://doi.org/10.1016/S0092-8674(00)81580-9CrossRefGoogle Scholar
  37. 37.
    Elgert KD (2009) Immunology: understanding the immune system, 2nd edn. Wiley-Blacwell, New JerseyGoogle Scholar
  38. 38.
    Song H, Nie X, Basu S, Cerny J (1998) Antibody feedback and somatic mutation in B cells: regulation of mutation by immune complexes with IgG antibody. Immunol Rev 162:211–218.  https://doi.org/10.1111/j.1600-065X.1998.tb01443.xCrossRefGoogle Scholar
  39. 39.
    Di Noia JM, Neuberger MS (2007) Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 76:1–22.  https://doi.org/10.1146/annurev.biochem.76.061705.090740CrossRefGoogle Scholar
  40. 40.
    Rajewsky K, Forster I, Cumano A (1987) Evolutionary and somatic selection of the antibody repertoire in the mouse. Science 238:1088–1094.  https://doi.org/10.1126/science.3317826CrossRefGoogle Scholar
  41. 41.
    Manis JP, Tian M, Alt FW (2002) Mechanism and control of class-switch recombination. Trends Immunol 23:31–39.  https://doi.org/10.1016/S1471-4906(01)02111-1CrossRefGoogle Scholar
  42. 42.
    Stavnezer J, Amemiya CT (2004) Evolution of isotype switching. Semin Immunol 16:257–275.  https://doi.org/10.1016/j.smim.2004.08.005CrossRefGoogle Scholar
  43. 43.
    De Silva NS, Klein U (2015) Dynamics of B cells in germinal centres. Nat Rev Immunol 15:137–148.  https://doi.org/10.1038/nri3804CrossRefGoogle Scholar
  44. 44.
    Muramatsu M, Kinoshita K, Fagarasan S et al (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553–563.  https://doi.org/10.1016/S0092-8674(00)00078-7CrossRefGoogle Scholar
  45. 45.
    Larson ED, Maizels N (2004) Transcription-coupled mutagenesis by the DNA deaminase AID. Genome Biol 5:211.  https://doi.org/10.1186/gb-2004-5-3-211CrossRefGoogle Scholar
  46. 46.
    Pham P, Bransteitter R, Petruska J, Goodman MF (2003) Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424:103–107.  https://doi.org/10.1038/nature01760CrossRefGoogle Scholar
  47. 47.
    Lin GG, Scott JG (2012) Germinal center organization and cellular dynamics. Immunity 100:130–134.  https://doi.org/10.1016/j.pestbp.2011.02.012.InvestigationsCrossRefGoogle Scholar
  48. 48.
    Lipman NS, Jackson LR, Trudel LJ, Weis-Garcia F (2005) Monoclonal versus polyclonal antibodies: distinguishing characteristics, applications, and information resources. ILAR J 46:258–268.  https://doi.org/10.1093/ilar.46.3.258CrossRefGoogle Scholar
  49. 49.
    Payne WJ, Marshall DL, Shockley RK, Martin WJ (1988) Clinical laboratory applications of monoclonal antibodies. Clin Microbiol Rev 1:313–329.  https://doi.org/10.1128/cmr.1.3.313CrossRefGoogle Scholar
  50. 50.
    Barbet J, Bardiès M, Bourgeois M et al (2012) In: Chames P (ed) Radiolabeled antibodies for cancer imaging and therapy BT – antibody engineering: methods and protocols, 2nd edn. Humana Press, Totowa, pp 681–697Google Scholar
  51. 51.
    Breedveld FC (2000) Therapeutic monoclonal antibodies. Lancet 355:735–740.  https://doi.org/10.1016/S0140-6736(00)01034-5CrossRefGoogle Scholar
  52. 52.
    Chames P, Van Regenmortel M, Weiss E, Baty D (2009) Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157:220–233.  https://doi.org/10.1111/j.1476-5381.2009.00190.xCrossRefGoogle Scholar
  53. 53.
    Winter G, Milstein C (1991) Man-made antibodies. Nature 349:293–299.  https://doi.org/10.1038/349293a0CrossRefGoogle Scholar
  54. 54.
    Khazaeli MB, Conry RM, LoBuglio AF (1994) Human immune response to monoclonal antibodies. J Immunother Emphasis Tumor Immunol 15:42–52Google Scholar
  55. 55.
    Almagro JC, Fransson J (2008) Humanization of antibodies. Front Biosci 13:1619–1633Google Scholar
  56. 56.
    Pavlou AK, Belsey MJ (2005) The therapeutic antibodies market to 2008. Eur J Pharm Biopharm 59:389–396.  https://doi.org/10.1016/j.ejpb.2004.11.007CrossRefGoogle Scholar
  57. 57.
    Schwarz EM, Ritchlin CT (2007) Clinical development of anti-RANKL therapy. Arthritis Res Ther 9:S7.  https://doi.org/10.1186/ar2171CrossRefGoogle Scholar
  58. 58.
    Teeling JL, French RR, Cragg MS et al (2004) Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 104:1793–1800.  https://doi.org/10.1182/blood-2004-01-0039CrossRefGoogle Scholar
  59. 59.
    Murphy AJ, Macdonald LE, Stevens S et al (2014) Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci 111:5153–5158.  https://doi.org/10.1073/pnas.1324022111CrossRefGoogle Scholar
  60. 60.
    Kennedy PJ, Oliveira C, Granja PL, Sarmento B (2017) Antibodies and associates: partners in targeted drug delivery. Pharmacol Ther 177:129–145.  https://doi.org/10.1016/j.pharmthera.2017.03.004CrossRefGoogle Scholar
  61. 61.
    Holliger P, Hudson PJ (2005) Engineered antibody fragments and the rise of single domains. Nat Biotechnol 23:1126–1136.  https://doi.org/10.1038/nbt1142CrossRefGoogle Scholar
  62. 62.
    Weir ANC, Nesbitt A, Chapman AP et al (2002) Formatting antibody fragments to mediate specific therapeutic functions. Biochem Soc Trans 30:512–516Google Scholar
  63. 63.
    Fischer N, Léger O (2007) Bispecific antibodies: molecules that enable novel therapeutic strategies. Pathobiology 74:3–14.  https://doi.org/10.1159/000101046CrossRefGoogle Scholar
  64. 64.
    Cuesta AM, Sánchez-Martín D, Sanz L et al (2009) In vivo tumor targeting and imaging with engineered trivalent antibody fragments containing collagen-derived sequences. PLoS One 4:e5381.  https://doi.org/10.1371/journal.pone.0005381CrossRefGoogle Scholar
  65. 65.
    Oliveira SS, Aires da Silva F, Lourenco S et al (2012) Assessing combinatorial strategies to multimerize libraries of single-domain antibodies. Biotechnol Appl Biochem 59:193–204.  https://doi.org/10.1002/bab.1011CrossRefGoogle Scholar
  66. 66.
    Thie H, Binius S, Schirrmann T et al (2009) Multimerization domains for antibody phage display and antibody production. N Biotechnol 26:314–321.  https://doi.org/10.1016/j.nbt.2009.07.005CrossRefGoogle Scholar
  67. 67.
    Lambert JM (2013) Drug-conjugated antibodies for the treatment of cancer. Br J Clin Pharmacol 76:248–262.  https://doi.org/10.1111/bcp.12044CrossRefGoogle Scholar
  68. 68.
    Casi G, Neri D (2012) Antibody–drug conjugates: basic concepts, examples and future perspectives. J Control Release 161:422–428.  https://doi.org/10.1016/J.JCONREL.2012.01.026CrossRefGoogle Scholar
  69. 69.
    Chudasama V, Maruani A, Caddick S (2016) Recent advances in the construction of antibody–drug conjugates. Nat Chem 8:114–119.  https://doi.org/10.1038/nchem.2415CrossRefGoogle Scholar
  70. 70.
    Abdollahpour-Alitappeh M, Lotfinia M, Gharibi T et al (2019) Antibody–drug conjugates (ADCs) for cancer therapy: strategies, challenges, and successes. J Cell Physiol 234:5628–5642.  https://doi.org/10.1002/jcp.27419CrossRefGoogle Scholar
  71. 71.
    Arruebo M, Valladares M, González-Fernández Á (2009) Antibody-conjugated nanoparticles for biomedical applications. J Nanomater 2009:1–24.  https://doi.org/10.1155/2009/439389CrossRefGoogle Scholar
  72. 72.
    Bertrand N, Wu J, Xu X et al (2014) Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 66:2–25.  https://doi.org/10.1016/J.ADDR.2013.11.009CrossRefGoogle Scholar
  73. 73.
    Krishnamurthy A, Jimeno A (2017) Bispecific antibodies for cancer therapy: a review. Pharmacol Ther.  https://doi.org/10.1016/j.pharmthera.2017.12.002Google Scholar
  74. 74.
    Nagorsen D, Bargou R, Rüttinger D et al (2009) Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma 50:886–891.  https://doi.org/10.1080/10428190902943077CrossRefGoogle Scholar
  75. 75.
    Baeuerle PA, Kufer P, Bargou R (2009) BiTE: teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther 11:22–30Google Scholar
  76. 76.
    Gross G, Eshhar Z (2016) Therapeutic potential of T cell chimeric antigen receptors (CARs) in cancer treatment: counteracting off-tumor toxicities for safe CAR T cell therapy. Annu Rev Pharmacol Toxicol 56:59–83.  https://doi.org/10.1146/annurev-pharmtox-010814-124844CrossRefGoogle Scholar
  77. 77.
    Pule M, Finney H, Lawson A (2003) Artificial T-cell receptor. Cytotherapy 5:211–226.  https://doi.org/10.1080/14653240310001488CrossRefGoogle Scholar
  78. 78.
    American Association for Cancer (2017) First-ever CAR T-cell therapy approved in U.S. Cancer Discov 7.  https://doi.org/10.1158/2159-8290.CD-NB2017-126
  79. 79.
    Grand View Research (2016) Monoclonal antibodies (mAbs) market size worth $138.6 billion by 2024Google Scholar
  80. 80.
    Elgundi Z, Reslan M, Cruz E et al (2016) The state-of-play and future of antibody therapeutics. Adv Drug Deliv Rev.  https://doi.org/10.1016/j.addr.2016.11.004Google Scholar
  81. 81.
    Bunnak P, Allmendinger R, Ramasamy SV et al (2016) Life-cycle and cost of goods assessment of fed-batch and perfusion-based manufacturing processes for mAbs. Biotechnol Prog 32:1324–1335.  https://doi.org/10.1002/btpr.2323CrossRefGoogle Scholar
  82. 82.
    Nieri P, Donadio D, Rossi S et al (2009) Antibodies for therapeutic uses and the evolution of biotechniques. Curr Med Chem 16:753–779.  https://doi.org/10.2174/092986709787458380CrossRefGoogle Scholar
  83. 83.
    Orlandi R, Gussow DH, Jones PT, Winter G (1989) Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc Natl Acad Sci 86:3833–3837.  https://doi.org/10.1073/pnas.86.10.3833CrossRefGoogle Scholar
  84. 84.
    Gussow D, Ward ES, Griffiths AD et al (1989) Generating binding activities from Escherichia coli by expression of a repertoire of immunoglobulin variable domains. Cold Spring Harb Symp Quant Biol 54:265–272.  https://doi.org/10.1101/SQB.1989.054.01.033CrossRefGoogle Scholar
  85. 85.
    McCafferty J, Griffiths AD, Winter G, Chiswell DJ (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348:552–554.  https://doi.org/10.1038/348552a0CrossRefGoogle Scholar
  86. 86.
    Hoogenboom HR (2005) Selecting and screening recombinant antibody libraries. Nat Biotechnol 23:1105–1116.  https://doi.org/10.1038/nbt1126CrossRefGoogle Scholar
  87. 87.
    Ponsel D, Neugebauer J, Ladetzki-Baehs K, Tissot K (2011) High affinity, developability and functional size: the holy grail of combinatorial antibody library generation. Molecules 16:3675–3700.  https://doi.org/10.3390/molecules16053675CrossRefGoogle Scholar
  88. 88.
    Adams JJ, Nelson B, Sidhu SS (2014) Recombinant genetic libraries and human monoclonal antibodies. Methods Mol Biol 1060:149–170.  https://doi.org/10.1007/978-1-62703-586-6_9CrossRefGoogle Scholar
  89. 89.
    Aires da Silva F, Corte-Real S, Goncalves J (2008) Recombinant antibodies as therapeutic agents. BioDrugs 22:301–314.  https://doi.org/10.2165/00063030-200822050-00003CrossRefGoogle Scholar
  90. 90.
    Hust M, Frenzel A, Meyer T et al (2012) Construction of human naive antibody gene libraries. In: Gene function analysis, methods in molecular biology. Humana Press, Totowa, pp 85–107Google Scholar
  91. 91.
    Vaughan TJ, Williams AJ, Pritchard K et al (1996) Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol 14:309–314.  https://doi.org/10.1038/nbt0396-309CrossRefGoogle Scholar
  92. 92.
    Soon Lim T, Khim Chan S (2016) Immune antibody libraries: manipulating the diverse immune repertoire for antibody discovery. Curr Pharm Des 22:6480–6489.  https://doi.org/10.2174/1381612822666160923111924CrossRefGoogle Scholar
  93. 93.
    Posner B, Lee I, Itoh T et al (1993) A revised strategy for cloning antibody gene fragments in bacteria. Gene 128:111–117.  https://doi.org/10.1016/0378-1119(93)90161-UCrossRefGoogle Scholar
  94. 94.
    Nuttall SD (2012) Overview and discovery of IgNARs and generation of VNARs. Methods Mol Biol 911:27–36.  https://doi.org/10.1007/978-1-61779-968-6_3CrossRefGoogle Scholar
  95. 95.
    Wesolowski J, Alzogaray V, Reyelt J et al (2009) Single domain antibodies: promising experimental and therapeutic tools in infection and immunity. Med Microbiol Immunol 198:157–174.  https://doi.org/10.1007/s00430-009-0116-7CrossRefGoogle Scholar
  96. 96.
    Adams JJ, Sidhu SS (2014) Synthetic antibody technologies. Curr Opin Struct Biol 24:1–9.  https://doi.org/10.1016/j.sbi.2013.11.003CrossRefGoogle Scholar
  97. 97.
    Hoogenboom HR, Winter G (1992) By-passing immunisation. J Mol Biol 227:381–388.  https://doi.org/10.1016/0022-2836(92)90894-PCrossRefGoogle Scholar
  98. 98.
    Yang HY, Kang KJ, Chung JE, Shim H (2009) Construction of a large synthetic human scFv library with six diversified CDRs and high functional diversity. Mol Cells 27:225–235.  https://doi.org/10.1007/s10059-009-0028-9CrossRefGoogle Scholar
  99. 99.
    Silacci M, Brack S, Schirru G et al (2005) Design, construction, and characterization of a large synthetic human antibody phage display library. Proteomics 5:2340–2350.  https://doi.org/10.1002/pmic.200401273CrossRefGoogle Scholar
  100. 100.
    Cunha-santos C, Figueira TN, Borrego P, Oliveira SS (2016) Development of synthetic light-chain antibodies as novel and potent HIV fusion inhibitors. AIDS 30(11):1691–1701Google Scholar
  101. 101.
    Tiller T, Schuster I, Deppe D et al (2013) A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties. MAbs 5:445–470.  https://doi.org/10.4161/mabs.24218CrossRefGoogle Scholar
  102. 102.
    Prassler J, Thiel S, Pracht C et al (2011) HuCAL PLATINUM, a synthetic fab library optimized for sequence diversity and superior performance in mammalian expression systems. J Mol Biol 413:261–278.  https://doi.org/10.1016/j.jmb.2011.08.012CrossRefGoogle Scholar
  103. 103.
    Shim H (2015) Synthetic approach to the generation of antibody diversity. BMB Rep 48:489–494.  https://doi.org/10.5483/BMBRep.2015.48.9.120CrossRefGoogle Scholar
  104. 104.
    Miersch S, Sidhu SS (2012) Synthetic antibodies: concepts, potential and practical considerations. Methods 57:486–498.  https://doi.org/10.1016/j.ymeth.2012.06.012CrossRefGoogle Scholar
  105. 105.
    Hoet RM, Cohen EH, Kent RB et al (2005) Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nat Biotechnol 23:344–348.  https://doi.org/10.1038/nbt1067CrossRefGoogle Scholar
  106. 106.
    Soderlind E, Strandberg L, Jirholt P et al (2000) Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat Biotechnol 18:852–856.  https://doi.org/10.1038/78458CrossRefGoogle Scholar
  107. 107.
    Hartwell L, Hood L, Goldberg M et al (2008) Genetics: from genes to genomes, 4th edn. McGraw Hill, New YorkGoogle Scholar
  108. 108.
    Bradbury ARM, Sidhu S, Dubel S, McCafferty J (2011) Beyond natural antibodies: the power of in vitro display technologies. Nat Biotechnol 29:245–254.  https://doi.org/10.1038/nbt.1791CrossRefGoogle Scholar
  109. 109.
    Barbas CF, Kang AS, Lerner RA, Benkovic SJ (1991) Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci 88:7978–7982.  https://doi.org/10.1073/pnas.88.18.7978CrossRefGoogle Scholar
  110. 110.
    Smith G (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228:1315–1317.  https://doi.org/10.1126/science.4001944CrossRefGoogle Scholar
  111. 111.
    Huang JX, Bishop-Hurley SL, Cooper MA (2012) Development of anti-infectives using phage display: biological agents against bacteria, viruses, and parasites. Antimicrob Agents Chemother 56:4569–4582.  https://doi.org/10.1128/AAC.00567-12CrossRefGoogle Scholar
  112. 112.
    Barbas CF (1995) Synthetic human antibodies. Nat Med 1:837–839.  https://doi.org/10.1038/340091a0CrossRefGoogle Scholar
  113. 113.
    Bain B, Brazil M (2003) Adalimumab. Nat Rev Drug Discov 2:693–694.  https://doi.org/10.1038/nrd1182CrossRefGoogle Scholar
  114. 114.
    Vendel MC, Favis M, Snyder WB et al (2012) Secretion from bacterial versus mammalian cells yields a recombinant scFv with variable folding properties. Arch Biochem Biophys 526:188–193.  https://doi.org/10.1016/j.abb.2011.12.018CrossRefGoogle Scholar
  115. 115.
    Lipovsek D, Plückthun A (2004) In-vitro protein evolution by ribosome display and mRNA display. J Immunol Methods 290:51–67.  https://doi.org/10.1016/j.jim.2004.04.008CrossRefGoogle Scholar
  116. 116.
    Ullman CG, Frigotto L, Cooley RN (2011) In vitro methods for peptide display and their applications. Brief Funct Genomics 10:125–134.  https://doi.org/10.1093/bfgp/elr010CrossRefGoogle Scholar
  117. 117.
    Doerner A, Rhiel L, Zielonka S, Kolmar H (2014) Therapeutic antibody engineering by high efficiency cell screening. FEBS Lett 588:278–287.  https://doi.org/10.1016/j.febslet.2013.11.025CrossRefGoogle Scholar
  118. 118.
    Black CB, Duensing TD, Trinkle LS, Dunlay RT (2011) Cell-based screening using high-throughput flow cytometry. Assay Drug Dev Technol 9:13–20.  https://doi.org/10.1089/adt.2010.0308CrossRefGoogle Scholar
  119. 119.
    Boder ET, Wittrup KD (1997) Yeast surface display for screening combinatorial polypeptide libraries. Nat Biotechnol 15:553–557.  https://doi.org/10.1038/nbt0697-553CrossRefGoogle Scholar
  120. 120.
    Cherf GM, Cochran JR (2015) Applications of yeast surface display for protein engineering. Yeast Surf Disp Methods Protoc Appl:155–175.  https://doi.org/10.1007/978-1-4939-2748-7_8Google Scholar
  121. 121.
    Koide S, Koide A, Lipovšek D (2012) Target-binding proteins based on the 10th human fibronectin type III domain (10 Fn3). Methods Enzymol 503:135–156.  https://doi.org/10.1016/B978-0-12-396962-0.00006-9CrossRefGoogle Scholar
  122. 122.
    Boder ET, Raeeszadeh-Sarmazdeh M, Price JV (2012) Engineering antibodies by yeast display. Arch Biochem Biophys 526:99–106.  https://doi.org/10.1016/j.abb.2012.03.009CrossRefGoogle Scholar
  123. 123.
    Zhou C, Jacobsen FW, Cai L et al (2010) Development of a novel mammalian cell surface antibody display platform. MAbs 2:508–518.  https://doi.org/10.4161/mabs.2.5.12970CrossRefGoogle Scholar
  124. 124.
    Mitchell Ho IP (2009) Mammalian cell display for antibody. Engineering 525:1–15.  https://doi.org/10.1007/978-1-59745-554-1CrossRefGoogle Scholar
  125. 125.
    Zhang H, Wilson IA, Lerner RA (2012) Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries. Proc Natl Acad Sci U S A 109:15728–15733.  https://doi.org/10.1073/pnas.1214275109CrossRefGoogle Scholar
  126. 126.
    Beerli RR, Bauer M, Buser RB et al (2008) Isolation of human monoclonal antibodies by mammalian cell display. Proc Natl Acad Sci U S A 105:14336–14341.  https://doi.org/10.1073/pnas.0805942105CrossRefGoogle Scholar
  127. 127.
    Walker JM (2012) Antibody engineering methods and protocols, 2nd edn. Humana Press, TotowaGoogle Scholar
  128. 128.
    Lu WC, Ellington AD (2013) In vitro selection of proteins via emulsion compartments. Methods 60:75–80.  https://doi.org/10.1016/j.ymeth.2012.03.008CrossRefGoogle Scholar
  129. 129.
    Tawfik DS, Griffiths AD (1998) Man-made cell-like compartments for molecular evolution. Nat Biotechnol 16:652–656.  https://doi.org/10.1038/nbt0798-652CrossRefGoogle Scholar
  130. 130.
    Kennedy PJ, Oliveira C, Granja PL, Sarmento B (2017) Monoclonal antibodies: technologies for early discovery and engineering. Crit Rev Biotechnol 0:1–15.  https://doi.org/10.1080/07388551.2017.1357002CrossRefGoogle Scholar
  131. 131.
    Lutz S (2011) Beyond directed evolution – semi-rational protein engineering and design. Curr Opin Biotechnol 21:734–743.  https://doi.org/10.1016/j.copbio.2010.08.011.BeyondCrossRefGoogle Scholar
  132. 132.
    Boder ET, Midelfort KS, Wittrup KD (2000) Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc Natl Acad Sci 97:10701–10705.  https://doi.org/10.1073/pnas.170297297CrossRefGoogle Scholar
  133. 133.
    Packer MS, Liu DR (2015) Methods for the directed evolution of proteins. Nat Rev Genet 16:379–394.  https://doi.org/10.1038/nrg3927CrossRefGoogle Scholar
  134. 134.
    Thie H, Voedisch B, Dübel S et al (2009) Affinity maturation by phage display. Methods Mol Biol 525:309–322.  https://doi.org/10.1007/978-1-59745-554-1_16CrossRefGoogle Scholar
  135. 135.
    Cadwell RC, Joyce GF (1994) Mutagenic PCR. PCR Methods Appl 3:S136–S140Google Scholar
  136. 136.
    Coia G, Hudson PJ, Irving RA (2001) Protein affinity maturation in vivo using E. coli mutator cells. J Immunol Methods 251:187–193.  https://doi.org/10.1016/S0022-1759(01)00300-3CrossRefGoogle Scholar
  137. 137.
    Marks JD, Griffiths AD, Malmqvist M et al (1992) By-passing immunization: building high affinity human antibodies by chain shuffling. Nat Biotechnol 10:779–783.  https://doi.org/10.1038/nbt0792-779CrossRefGoogle Scholar
  138. 138.
    Yang W-P, Green K, Pinz-Sweeney S et al (1995) CDR walking mutagenesis for the affinity maturation of a potent human anti-HIV-1 antibody into the picomolar range. J Mol Biol 254:392–403.  https://doi.org/10.1006/jmbi.1995.0626CrossRefGoogle Scholar
  139. 139.
    Wang HH, Isaacs FJ, Carr PA et al (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460:894–898.  https://doi.org/10.1038/nature08187CrossRefGoogle Scholar
  140. 140.
    Hartl DL (2015) What can we learn from fitness landscapes? Curr Opin Microbiol:213–223.  https://doi.org/10.1007/978-1-62703-673-3Google Scholar
  141. 141.
    Leemhuis H, Stein V, Griffiths AD, Hollfelder F (2005) New genotype-phenotype linkages for directed evolution of functional proteins. Curr Opin Struct Biol 15:472–478.  https://doi.org/10.1016/j.sbi.2005.07.006CrossRefGoogle Scholar
  142. 142.
    Arnold F, Georgiou G (2003) Directed evolution library creation. Humana Press, TotowaGoogle Scholar
  143. 143.
    Smith SA, Crowe JE (2015) Use of human hybridoma technology to isolate human monoclonal antibodies. Microbiol Spectr 3:1–12.  https://doi.org/10.1128/microbiolspec.AIDCrossRefGoogle Scholar
  144. 144.
    Chan CEZ, Lim APC, MacAry PA, Hanson BJ (2014) The role of phage display in therapeutic antibody discovery. Int Immunol 26:649–657.  https://doi.org/10.1093/intimm/dxu082CrossRefGoogle Scholar
  145. 145.
    Ho M, Pastan I (2009) Display and selection of scFv antibodies on HEK-293T cells. In: Antibody phage display: methods and protocols, 2nd edn. Humana Press, Totowa, pp 99–113Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.LeanBioProBarcelonaSpain
  2. 2.iMed – Research Institute for Medicines, Faculty of Pharmacy at University of LisbonLisbonPortugal

Personalised recommendations