Antibody Phage Display

Handbook of Therapeutic Antibodies: Second Edition

Volumn 1-4, Issue , 2014, Pages 43-76

  Hust, Michael ^a   Frenzel, André ^a   Tomszak, Florian ^a   Kügler, Jonas ^a,b   Dübel, Stefan ^a  

^a TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^b MAb factory GmbH   (Germany)

Author keywords

Antibody gene library; In vitro selection; Panning; Phage display; Recombinant antibody; Single chain Fv (scFv)

Indexed keywords

ANTIBODY GENES; IN-VITRO; PANNING; PHAGE DISPLAY; RECOMBINANT ANTIBODY; SINGLE-CHAIN FV;

ANTIBODIES;

EID: 84940847552     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527682423.ch3     Document Type: Chapter

References (177)

1. Von Behring, E. and Kitasato, S. (1890) Über das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. Deutsch. Med. Wochenzeitschrift, 16, 1113-1114.
2. Köhler, G. and Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 256, 495-497.
3. Courtenay-Luck, N.S., Epenetos, A.A., Moore, R., Larche, M., Pectasides, D., Dhokia, B., and Ritter, M.A. (1986) Development of primary and secondary immune responses to mouse monoclonal antibodies used in the diagnosis and therapy of malignant neoplasms. Cancer Res., 46, 6489-6493.
4. Tjandra, J.J., Ramadi, L., and McKenzie, I.F. (1990) Development of human anti-murine antibody (HAMA) response in patients. Immunol. Cell Biol., 68 (Pt. 6), 367-376.
5. Almagro, J.C. and Fransson, J. (2008) Humanization of antibodies. Front. Biosci., 13, 1619-1633.
6. Hwang, W.Y.K. and Foote, J. (2005) Immunogenicity of engineered antibodies. Methods, 36, 3-10.
7. Kashmiri, S.V.S., De Pascalis, R., Gonzales, N.R., and Schlom, J. (2005) SDR grafting - a new approach to antibody humanization. Methods, 36, 25-34.
8. Studnicka, G.M., Soares, S., Better, M., Williams, R.E., Nadell, R., and Horwitz, A.H. (1994) Humanengineered monoclonal antibodies retain full specific binding activity by preserving non-CDR complementaritymodulating residues. Protein Eng., 7, 805-814.
9. Li, J., Sai, T., Berger, M., Chao, Q., Davidson, D., Deshmukh, G., Drozdowski, B., Ebel, W., Harley, S., Henry, M., Jacob, S., Kline, B., Lazo, E., Rotella, F., Routhier, E., Rudolph, K., Sage, J., Simon, P., Yao, J., Zhou, Y., Kavuru, M., Bonfield, T., Thomassen, M.J., Sass, P.M., Nicolaides, N.C., and Grasso, L. (2006) Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proc. Natl. Acad. Sci. U.S.A., 103, 3557-3562.
10. Shirahata, S., Katakura, Y., and Teruya, K. (1998) Cell hybridization, hybridomas, and human hybridomas. Methods Cell Biol., 57, 111-145.
11. Siegel, D.L. (2002) Recombinant monoclonal antibody technology. Transfus. Clin. Biol., 9, 15-22.
12. Smith, S.A., Zhou, Y., Olivarez, N.P., Broadwater, A.H., de Silva, A.M., and Crowe, J.E. Jr., (2012) Persistence of circulating memory B cell clones with potential for dengue virus disease enhancement for decades following infection. J. Virol., 86, 2665-2675.
13. Fishwild, D.M., O'Donnell, S.L., Bengoechea, T., Hudson, D.V., Harding, F., Bernhard, S.L., Jones, D., Kay, R.M., Higgins, K.M., Schramm, S.R., and Lonberg, N. (1996) Highavidity human IgG kappa monoclonal antibodies from a novel strain of minilocus transgenic mice. Nat. Biotechnol., 14, 845-851.
14. Jakobovits, A. (1995) Production of fully human antibodies by transgenic mice. Curr. Opin. Biotechnol., 6, 561-566.
15. Kuroiwa, Y., Kasinathan, P., Choi, Y.J., Naeem, R., Tomizuka, K., Sullivan, E.J., Knott, J.G., Duteau, A., Goldsby, R.A., Osborne, B.A., Ishida, I., and Robl, J.M. (2002) Cloned transchromosomic calves producing human immunoglobulin. Nat. Biotechnol., 20, 889-894.
16. Kuroiwa, Y., Kasinathan, P., Sathiyaseelan, T., Jiao, J., Matsushita, H., Sathiyaseelan, J., Wu, H., Mellquist, J., Hammitt, M., Koster, J., Kamoda, S., Tachibana, K., Ishida, I., and Robl, J.M. (2009) Antigenspecific human polyclonal antibodies from hyperimmunized cattle. Nat. Biotechnol., 27, 173-181.
17. Lonberg, N. and Huszar, D. (1995) Human antibodies from transgenic mice. Int. Rev. Immunol., 13, 65-93.
18. Weiner, L.M. (2006) Fully human therapeutic monoclonal antibodies. J. Immunother., 29, 1-9.
19. Winter, G., Griffiths, A.D., Hawkins, R.E., and Hoogenboom, H.R. (1994) Making antibodies by phage display technology. Annu. Rev. Immunol., 12, 433-455.
20. Winter, G. and Milstein, C. (1991) Man-made antibodies. Nature, 349, 293-299.
21. Fleetwood, F., Devoogdt, N., Pellis, M., Wernery, U., Muyldermans, S., Ståhl, S., and Löfblom, J. (2012) Surface display of a single-domain antibody library on Gram-positive bacteria. Cell. Mol. Life Sci., 526 (2), 114-123.
22. Fuchs, P., Breitling, F., Dübel, S., Seehaus, T., and Little, M. (1991) Targeting recombinant antibodies to the surface of Escherichia coli: fusion to a peptidoglycan associated lipoprotein. Biotechnology (N.Y.), 9, 1369-1372.
23. Jostock, T. and Dübel, S. (2005) Screening of molecular repertoires by microbial surface display. Comb. Chem. High Throughput Screen., 8, 127-133.
24. Boder, E.T. and Wittrup, K.D. (1997) Yeast surface display for screening combinatorial polypeptide libraries. Nat. Biotechnol., 15, 553-557.
25. Feldhaus, M.J. and Siegel, R.W. (2004) Yeast display of antibody fragments: a discovery and characterization platform. J. Immunol. Methods, 290, 69-80.
26. Walker, L.M., Bowley, D.R., and Burton, D.R. (2009) Efficient recovery of high-affinity antibodies from a single-chain Fab yeast display library. J. Mol. Biol., 389, 365-375.
27. Hanes, J. and Plückthun, A. (1997) In vitro selection and evolution of functional proteins by using ribosome display. Proc. Natl. Acad. Sci. U.S.A., 94, 4937-4942.
28. He, M. and Taussig, M.J. (1997) Antibody-ribosome-mRNA (ARM) complexes as efficient selection particles for in vitro display and evolution of antibody combining sites. Nucleic Acids Res., 25, 5132-5134.
29. He, M. and Taussig, M.J. (2008) Selection of recombinant antibodies by eukaryotic ribosome display. Methods Mol. Biol., 484, 193-205.
30. Schaffitzel, C., Hanes, J., Jermutus, L., and Plückthun, A. (1999) Ribosome display: an in vitro method for selection and evolution of antibodies from libraries. J. Immunol. Methods, 231, 119-135.
31. Roberts, R.W. and Szostak, J.W. (1997) RNA-peptide fusions for the in vitro selection of peptides and proteins. Proc. Natl. Acad. Sci. U.S.A., 94, 12297-12302.
32. Hust, M. and Dübel, S. (2005) Phage display vectors for the in vitro generation of human antibody fragments. Methods Mol. Biol., 295, 71-96.
33. Danner, S. and Belasco, J.G. (2001) T7 phage display: a novel genetic selection system for cloning RNA-binding proteins from cDNA libraries. Proc. Natl. Acad. Sci. U.S.A., 98, 12954-12959.
34. Huse, W.D., Sastry, L., Iverson, S.A., Kang, A.S., Alting-Mees, M., Burton, D.R., Benkovic, S.J., and Lerner, R.A. (1989) Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science, 246, 1275-1281.
35. Kang, A.S., Jones, T.M., and Burton, D.R. (1991) Antibody redesign by chain shuffling from random combinatorial immunoglobulin libraries. Proc. Natl. Acad. Sci. U.S.A., 88, 11120-11123.
36. Mullinax, R.L., Gross, E.A., Amberg, J.R., Hay, B.N., Hogrefe, H.H., Kubitz, M.M., Greener, A., Alting-Mees, M., Ardourel, D., and Short, J.M. (1990) Identification of human antibody fragment clones specific for tetanus toxoid in a bacteriophage lambda immunoexpression library. Proc. Natl. Acad. Sci. U.S.A., 87, 8095-8099.
37. Smith, G.P. (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science, 228, 1315-1317.
38. Skerra, A. and Plückthun, A. (1988) Assembly of a functional immunoglobulin Fv fragment in Escherichia coli. Science, 240, 1038-1041.
39. Barbas, C.F., Kang, A.S., Lerner, R.A., and Benkovic, S.J. (1991) Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc. Natl. Acad. Sci. U.S.A., 88, 7978-7982.
40. Breitling, F., Dübel, S., Seehaus, T., Klewinghaus, I., and Little, M. (1991) A surface expression vector for antibody screening. Gene, 104, 147-153.
41. Clackson, T., Hoogenboom, H.R., Griffiths, A.D., and Winter, G. (1991) Making antibody fragments using phage display libraries. Nature, 352, 624-628.
42. Hoogenboom, H.R., Griffiths, A.D., Johnson, K.S., Chiswell, D.J., Hudson, P., and Winter, G. (1991) Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Res., 19, 4133-4137.
43. McCafferty, J., Griffiths, A.D., Winter, G., and Chiswell, D.J. (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature, 348, 552-554.
44. Dübel, S., Stoevesandt, O., Taussig, M.J., and Hust, M. (2010) Generating recombinant antibodies to the complete human proteome. Trends Biotechnol., 28, 333-339.
45. Hoet, R.M., Cohen, E.H., Kent, R.B., Rookey, K., Schoonbroodt, S., Hogan, S., Rem, L., Frans, N., Daukandt, M., Pieters, H., van Hegelsom, R., Neer, N.C., Nastri, H.G., Rondon, I.J., Leeds, J.A., Hufton, S.E., Huang, L., Kashin, I., Devlin, M., Kuang, G., Steukers, M., Viswanathan, M., Nixon, A.E., Sexton, D.J., Hoogenboom, H.R., and Ladner, R.C. (2005) Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nat. Biotechnol., 23, 344-348.
46. Holt, L.J., Herring, C., Jespers, L.S., Woolven, B.P., and Tomlinson, I.M. (2003) Domain antibodies: proteins for therapy. Trends Biotechnol., 21, 484-490.
47. Mazor, Y., Van Blarcom, T., Mabry, R., Iverson, B.L., and Georgiou, G. (2007) Isolation of engineered, full-length antibodies from libraries expressed in Escherichia coli. Nat. Biotechnol., 25, 563-565.
48. Simmons, L.C., Reilly, D., Klimowski, L., Raju, T.S., Meng, G., Sims, P., Hong, K., Shields, R.L., Damico, L.A., Rancatore, P., and Yansura, D.G. (2002) Expression of full-length immunoglobulins in Escherichia coli: rapid and efficient production of aglycosylated antibodies. J. Immunol. Methods, 263, 133-147.
49. Dueñas, M. and Borrebaeck, C.A. (1995) Novel helper phage design:intergenic region affects the assembly of bacteriophages and the size of antibody libraries. FEMS Microbiol. Lett., 125, 317-321.
50. Griffiths, A.D., Malmqvist, M., Marks, J.D., Bye, J.M., Embleton, M.J., McCafferty, J., Baier, M., Holliger, K.P., Gorick, B.D., and Hughes-Jones, N.C. (1993) Human anti-self antibodies with high specificity from phage display libraries. EMBO J., 12, 725-734.
51. Rakonjac, J., Jovanovic, G., and Model, P. (1997) Filamentous phage infectionmediated gene expression: construction and propagation of the gIII deletion mutant helper phage R408d3. Gene, 198, 99-103.
52. Chasteen, L., Ayriss, J., Pavlik, P., and Bradbury, A.R.M. (2006) Eliminating helper phage from phage display. Nucleic Acids Res., 34, e145.
53. Nelson, F.K., Friedman, S.M., and Smith, G.P. (1981) Filamentous phage DNA cloning vectors: a noninfective mutant with a nonpolar deletion in gene III. Virology, 108, 338-350.
54. Rondot, S., Koch, J., Breitling, F., and Dübel, S. (2001) A helper phage to improve single-chain antibody presentation in phage display. Nat. Biotechnol., 19, 75-78.
55. Soltes, G., Hust, M., Ng, K.K.Y., Bansal, A., Field, J., Stewart, D.I.H., Dübel, S., Cha, S., and Wiersma, E.J. (2007) On the influence of vector design on antibody phage display. J. Biotechnol., 127, 626-637.
56. Hust, M., Meyer, T., Voedisch, B., Rülker, T., Thie, H., El-Ghezal, A., Kirsch, M.I., Schütte, M., Helmsing, S., Meier, D., Schirrmann, T., and Dübel, S. (2011) A human scFv antibody generation pipeline for proteome research. J. Biotechnol., 152, 159-170.
57. Schirrmann, T. and Hust, M. (2010) Construction of human antibody gene libraries and selection of antibodies by phage display. Methods Mol. Biol., 651, 177-209.
58. Parmley, S.F. and Smith, G.P. (1988) Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene, 73, 305-318.
59. Hawlisch, H., Müller, M., Frank, R., Bautsch, W., Klos, A., and Köhl, J. (2001) Site-specific anti-C3a receptor single-chain antibodies selected by differential panning on cellulose sheets. Anal. Biochem., 293, 142-145.
60. Moghaddam, A., Borgen, T., Stacy, J., Kausmally, L., Simonsen, B., Marvik, O.J., Brekke, O.H., and Braunagel, M. (2003) Identification of scFv antibody fragments that specifically recognise the heroin metabolite 6-monoacetylmorphine but not morphine. J. Immunol. Methods, 280, 139-155.
61. Hust, M., Maiss, E., Jacobsen, H.-J., and Reinard, T. (2002) The production of a genus-specific recombinant antibody (scFv) using a recombinant potyvirus protease. J. Virological Methods, 106, 225-233.
62. Goffinet, M., Chinestra, P., Lajoie-Mazenc, I., Medale-Giamarchi, C., Favre, G., and Faye, J.-C. (2008) Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection. BMC Biotechnol., 8, 34.
63. Kaku, Y., Noguchi, A., Okutani, A., Inoue, S., Tanabayashi, K., Yamamoto, Y., Hotta, A., Suzuki, M., Sugiura, N., and Yamada, A. (2012) Altered specificity of single-chain antibody fragments bound to pandemic H1N1-2009 influenza virus after conversion of the phage-bound to the soluble form. BMC Res. Notes, 5, 483.
64. Lillo, A.M., Ayriss, J.E., Shou, Y., Graves, S.W., and Bradbury, A.R.M. (2011) Development of phage-based single chain Fv antibody reagents for detection of Yersinia pestis. PLoS One, 6, e27756.
65. Buckler, D.R., Park, A., Viswanathan, M., Hoet, R.M., and Ladner, R.C. (2008) Screening isolates from antibody phage-display libraries. Drug Discov. Today, 13, 318-324.
66. Hallborn, J. and Carlsson, R. (2002) Automated screening procedure for high-throughput generation of antibody fragments. Biotechniques, (Suppl), 30-37.
67. Konthur, Z., Hust, M., and Dübel, S. (2005) Perspectives for systematic in vitro antibody generation. Gene, 364, 19-29.
68. Jostock, T., Vanhove, M., Brepoels, E., Van Gool, R., Daukandt, M., Wehnert, A., Van Hegelsom, R., Dransfield, D., Sexton, D., Devlin, M., Ley, A., Hoogenboom, H., and Müllberg, J. (2004) Rapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries. J. Immunol. Methods, 289, 65-80.
69. Liang, M., Dübel, S., Li, D., Queitsch, I., Li, W., and Bautz, E.K. (2001) Baculovirus expression cassette vectors for rapid production of complete human IgG from phage display selected antibody fragments. J. Immunol. Methods, 247, 119-130.
70. Schirrmann, T., Al-Halabi, L., Dübel, S., and Hust, M. (2008) Production systems for recombinant antibodies. Front. Biosci., 13, 4576-4594.
71. Thie, H., Toleikis, L., Li, J., von Wasielewski, R., Bastert, G., Schirrmann, T., Esteves, I.T., Behrens, C.K., Fournes, B., Fournier, N., de Romeuf, C., Hust, M., and Dübel, S. (2011) Rise and fall of an anti-MUC1 specific antibody. PLoS One, 6, e15921.
72. Finlay, W.J., Cunningham, O., Lambert, M.A., Darmanin-Sheehan, A., Liu, X., Fennell, B.J., Mahon, C.M., Cummins, E., Wade, J.M., O'Sullivan, C.M., Tan, X.Y., Piche, N., Pittman, D.D., Paulsen, J., Tchistiakova, L., Kodangattil, S., Gill, D., and Hufton, S.E. (2009) Affinity maturation of a humanized rat antibody for anti-RAGE therapy: comprehensive mutagenesis reveals a high level of mutational plasticity both inside and outside the complementarity-determining regions. J. Mol. Biol., 388, 541-558.
73. Kobayashi, N., Oyama, H., Kato, Y., Goto, J., Söderlind, E., and Borrebaeck, C.A.K. (2010) Two-step in vitro antibody affinity maturation enables estradiol-17beta assays with more than 10-fold higher sensitivity. Anal. Chem., 82, 1027-1038.
74. Thie, H., Voedisch, B., Dübel, S., Hust, M., and Schirrmann, T. (2009) Affinity maturation by phage display. Methods Mol. Biol., 525, 309-322.
75. Paschke, M., Zahn, G., Warsinke, A., and Höhne, W. (2001) New series of vectors for phage display and prokaryotic expression of proteins. Biotechniques, 30, 720-724, 726.
76. Iba, Y., Ito, W., and Kurosawa, Y. (1997) Expression vectors for the introduction of highly diverged sequences into the six complementaritydetermining regions of an antibody. Gene, 194, 35-46.
77. Krebber, A., Bornhauser, S., Burmester, J., Honegger, A., Willuda, J., Bosshard, H.R., and Plückthun, A. (1997) Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system. J. Immunol. Methods, 201, 35-55.
78. Haidaris, C.G., Malone, J., Sherrill, L.A., Bliss, J.M., Gaspari, A.A., Insel, R.A., and Sullivan, M.A. (2001) Recombinant human antibody single chain variable fragments reactive with Candida albicans surface antigens. J. Immunol. Methods, 257, 185-202.
79. Hofer, T., Tangkeangsirisin, W., Kennedy, M.G., Mage, R.G., Raiker, S.J., Venkatesh, K., Lee, H., Giger, R.J., and Rader, C. (2007) Chimeric rabbit/human Fab and IgG specific for members of the Nogo-66 receptor family selected for species cross-reactivity with an improved phage display vector. J. Immunol. Methods, 318, 75-87.
80. McCafferty, J., Fitzgerald, K.J., Earnshaw, J., Chiswell, D.J., Link, J., Smith, R., and Kenten, J. (1994) Selection and rapid purification of murine antibody fragments that bind a transition-state analog by phage display. Appl. Biochem. Biotechnol., 47, 157-171; discussion 171-173.
81. De Haard, H.J., van Neer, N., Reurs, A., Hufton, S.E., Roovers, R.C., Henderikx, P., de Bruïne, A.P., Arends, J.W., and Hoogenboom, H.R. (1999) A large non-immunized human Fab fragment phage library that permits rapid isolation and kinetic analysis of high affinity antibodies. J. Biol. Chem., 274, 18218-18230.
82. Solforosi, L., Mancini, N., Canducci, F., Clementi, N., Sautto, G.A., Diotti, R.A., Clementi, M., and Burioni, R. (2012) A phage display vector optimized for the generation of human antibody combinatorial libraries and the molecular cloning of monoclonal antibody fragments. New Microbiol., 35, 289-294.
83. Barbas, C.F., Burton, D.R., Scott, J.K., and Silverman, G.J. (2001) Phage Display:A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York.
84. Tsurushita, N., Fu, H., and Warren, C. (1996) Phage display vectors for in vivo recombination of immunoglobulin heavy and light chain genes to make large combinatorial libraries. Gene, 172, 59-63.
85. Sblattero, D. and Bradbury, A. (2000) Exploiting recombination in single bacteria to make large phage antibody libraries. Nat. Biotechnol., 18, 75-80.
86. Garrard, L.J., Yang, M., O'Connell, M.P., Kelley, R.F., and Henner, D.J. (1991) Fab assembly and enrichment in a monovalent phage display system. Biotechnology (N.Y.), 9, 1373-1377.
87. Pini, A., Viti, F., Santucci, A., Carnemolla, B., Zardi, L., Neri, P., and Neri, D. (1998) Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel. J. Biol. Chem., 273, 21769-21776.
88. Viti, F., Nilsson, F., Demartis, S., Huber, A., and Neri, D. (2000) Design and use of phage display libraries for the selection of antibodies and enzymes. Methods Enzymol, 326, 480-505.
89. Söderlind, E., Lagerkvist, A.C., Dueñas, M., Malmborg, A.C., Ayala, M., Danielsson, L., and Borrebaeck, C.A. (1993) Chaperonin assisted phage display of antibody fragments on filamentous bacteriophages. Biotechnology (N.Y.), 11, 503-507.
90. Kobayashi, N., Söderlind, E., and Borrebaeck, C.A. (1997) Analysis of assembly of synthetic antibody fragments:expression of functional scFv with predefined specificity. Biotechniques, 23, 500-503.
91. Jirholt, P., Ohlin, M., Borrebaeck, C.A., and Söderlind, E. (1998) Exploiting sequence space: shuffling in vivo formed complementarity determining regions into a master framework. Gene, 215, 471-476.
92. Orum, H., Andersen, P.S., Oster, A., Johansen, L.K., Riise, E., Bjørnvad, M., Svendsen, I., and Engberg, J. (1993) Efficient method for constructing comprehensive murine Fab antibody libraries displayed on phage. Nucleic Acids Res., 21, 4491-4498.
93. Dziegiel, M., Nielsen, L.K., Andersen, P.S., Blancher, A., Dickmeiss, E., and Engberg, J. (1995) Phage display used for gene cloning of human recombinant antibody against the erythrocyte surface antigen, rhesus D. J. Immunol. Methods, 182, 7-19.
94. Engberg, J., Andersen, P.S., Nielsen, L.K., Dziegiel, M., Johansen, L.K., and Albrechtsen, B. (1996) Phage-display libraries of murine and human antibody Fab fragments. Mol. Biotechnol., 6, 287-310.
95. Morino, K., Katsumi, H., Akahori, Y., Iba, Y., Shinohara, M., Ukai, Y., Kohara, Y., and Kurosawa, Y. (2001) Antibody fusions with fluorescent proteins: a versatile reagent for profiling protein expression. J. Immunol. Methods, 257, 175-184.
96. Zahn, G., Skerra, A., and Höhne, W. (1999) Investigation of a tetracyclineregulated phage display system. Protein Eng., 12, 1031-1034.
97. Hust, M., Jostock, T., Menzel, C., Voedisch, B., Mohr, A., Brenneis, M., Kirsch, M.I., Meier, D., and Dübel, S. (2007) Single chain Fab (scFab) fragment. BMC Biotechnol., 7, 14.
98. Hoogenboom, H.R. and Winter, G. (1992) By-passing immunisation. Human antibodies from synthetic repertoires of germline VH gene segments rearranged in vitro. J. Mol. Biol., 227, 381-388.
99. Finnern, R., Pedrollo, E., Fisch, I., Wieslander, J., Marks, J.D., Lockwood, C.M., and Ouwehand, W.H. (1997) Human autoimmune anti-proteinase 3 scFv from a phage display library. Clin. Exp. Immunol., 107, 269-281.
100. Rojas, G., Almagro, J.C., Acevedo, B., and Gavilondo, J.V. (2002) Phage antibody fragments library combining a single human light chain variable region with immune mouse heavy chain variable regions. J. Biotechnol., 94, 287-298.
101. Den, W., Sompuram, S.R., Sarantopoulos, S., and Sharon, J. (1999) A bidirectional phage display vector for the selection and mass transfer of polyclonal antibody libraries. J. Immunol. Methods, 222, 45-57.
102. Ge, L., Knappik, A., Pack, P., Freund, C., and Plückthun, A. (1995) Antibody Engineering, Oxford University Press, New York, pp. 229-266.
103. Baek, H., Suk, K., Kim, Y., and Cha, S. (2002) An improved helper phage system for efficient isolation of specific antibody molecules in phage display. Nucleic Acids Res., 30, e18.
104. Goletz, S., Christensen, P.A., Kristensen, P., Blohm, D., Tomlinson, I., Winter, G., and Karsten, U. (2002) Selection of large diversities of antiidiotypic antibody fragments by phage display. J. Mol. Biol., 315, 1087-1097.
105. Garrard, L.J. and Henner, D.J. (1993) Selection of an anti-IGF-1 Fab from a Fab phage library created by mutagenesis of multiple CDR loops. Gene, 128, 103-109.
106. Geoffroy, F., Sodoyer, R., and Aujame, L. (1994) A new phage display system to construct multicombinatorial libraries of very large antibody repertoires. Gene, 151, 109-113.
107. Pansri, P., Jaruseranee, N., Rangnoi, K., Kristensen, P., and Yamabhai, M. (2009) A compact phage display human scFv library for selection of antibodies to a wide variety of antigens. BMC Biotechnol., 9, 6.
108. Knappik, A., Ge, L., Honegger, A., Pack, P., Fischer, M., Wellnhofer, G., Hoess, A., Wölle, J., Plückthun, A., and Virnekäs, B. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J. Mol. Biol., 296, 57-86.
109. Christ, D., Famm, K., and Winter, G. (2006) Tapping diversity lost in transformations--in vitro amplification of ligation reactions. Nucleic Acids Res., 34, e108.
110. Lee, C.V., Sidhu, S.S., and Fuh, G. (2004) Bivalent antibody phage display mimics natural immunoglobulin. J. Immunol. Methods, 284, 119-132.
111. Schofield, D.J., Pope, A.R., Clementel, V., Buckell, J., Chapple, S.D., Clarke, K.F., Conquer, J.S., Crofts, A.M., Crowther, S.R.E., Dyson, M.R., Flack, G., Griffin, G.J., Hooks, Y., Howat, W.J., Kolb-Kokocinski, A., Kunze, S., Martin, C.D., Maslen, G.L., Mitchell, J.N., O'Sullivan, M., Perera, R.L., Roake, W., Shadbolt, S.P., Vincent, K.J., Warford, A., Wilson, W.E., Xie, J., Young, J.L., and McCafferty, J. (2007) Application of phage display to high throughput antibody generation and characterization. Genome Biol., 8, R254.
112. Neri, P., Shigemori, N., Hamada-Tsutsumi, S., Tsukamoto, K., Arimitsu, H., Shimizu, T., Akahori, Y., Kurosawa, Y., and Tsuji, T. (2011) Single chain variable fragment antibodies against Shiga toxins isolated from a human antibody phage display library. Vaccine, 29, 5340-5346.
113. Akamatsu, Y., Cole, M.S., Tso, J.Y., and Tsurushita, N. (1993) Construction of a human Ig combinatorial library from genomic V segments and synthetic CDR3 fragments. J. Immunol., 151, 4651-4659.
114. Li, Y., Cockburn, W., Kilpatrick, J.B., and Whitelam, G.C. (2000) High affinity ScFvs from a single rabbit immunized with multiple haptens. Biochem. Biophys. Res. Commun., 268, 398-404.
115. Dübel, S., Breitling, F., Fuchs, P., Braunagel, M., Klewinghaus, I., and Little, M. (1993) A family of vectors for surface display and production of antibodies. Gene, 128, 97-101.
116. Welschof, M., Terness, P., Kipriyanov, S.M., Stanescu, D., Breitling, F., Dörsam, H., Dübel, S., Little, M., and Opelz, G. (1997) The antigen-binding domain of a human IgG-anti-F(ab')2 autoantibody. Proc. Natl. Acad. Sci. U.S.A., 94, 1902-1907.
117. Lei, S.P., Lin, H.C., Wang, S.S., Callaway, J., and Wilcox, G. (1987) Characterization of the Erwinia carotovora pelB gene and its product pectate lyase. J. Bacteriol., 169, 4379-4383.
118. Kirsch, M., Zaman, M., Meier, D., Dübel, S., and Hust, M. (2005) Parameters affecting the display of antibodies on phage. J. Immunol. Methods, 301, 173-185.
119. Steiner, D., Forrer, P., and Plückthun, A. (2008) Efficient selection of DARPins with sub-nanomolar affinities using SRP phage display. J. Mol. Biol., 382, 1211-1227.
120. Thie, H., Schirrmann, T., Paschke, M., Dübel, S., and Hust, M. (2008) SRP and Sec pathway leader peptides for antibody phage display and antibody fragment production in E. coli. Nat. Biotechnol., 25, 49-54.
121. Bird, R.E., Hardman, K.D., Jacobson, J.W., Johnson, S., Kaufman, B.M., Lee, S.M., Lee, T., Pope, S.H., Riordan, G.S., and Whitlow, M. (1988) Singlechain antigen-binding proteins. Science, 242, 423-426.
122. Bird, R.E. and Walker, B.W. (1991) Single chain antibody variable regions. Trends Biotechnol., 9, 132-137.
123. Huston, J.S., Levinson, D., Mudgett-Hunter, M., Tai, M.S., Novotný, J., Margolies, M.N., Ridge, R.J., Bruccoleri, R.E., Haber, E., and Crea, R. (1988) Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A., 85, 5879-5883.
124. Little, M., Welschof, M., Braunagel, M., Hermes, I., Christ, C., Keller, A., Rohrbach, P., Kürschner, T., Schmidt, S., Kleist, C., and Terness, P. (1999) Generation of a large complex antibody library from multiple donors. J. Immunol. Methods, 231, 3-9.
125. Løset, G.A., Løbersli, I., Kavlie, A., Stacy, J.E., Borgen, T., Kausmally, L., Hvattum, E., Simonsen, B., Hovda, M.B., and Brekke, O.H. (2005) Construction, evaluation and refinement of a large human antibody phage library based on the IgD and IgM variable gene repertoire. J. Immunol. Methods, 299, 47-62.
126. Sheets, M.D., Amersdorfer, P., Finnern, R., Sargent, P., Lindquist, E., Schier, R., Hemingsen, G., Wong, C., Gerhart, J.C., Marks, J.D., and Lindqvist, E. (1998) Efficient construction of a large nonimmune phage antibody library: the production of high-affinity human single-chain antibodies to protein antigens. Proc. Natl. Acad. Sci. U.S.A., 95, 6157-6162.
127. Griffiths, A.D., Williams, S.C., Hartley, O., Tomlinson, I.M., Waterhouse, P., Crosby, W.L., Kontermann, R.E., Jones, P.T., Low, N.M., and Allison, T.J. (1994) Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO J., 13, 3245-3260.
128. Marks, J.D., Hoogenboom, H.R., Bonnert, T.P., McCafferty, J., Griffiths, A.D., and Winter, G. (1991) By-passing immunization. Human antibodies from V-gene libraries displayed on phage. J. Mol. Biol., 222, 581-597.
129. Martin, C.D., Rojas, G., Mitchell, J.N., Vincent, K.J., Wu, J., McCafferty, J., and Schofield, D.J. (2006) A simple vector system to improve performance and utilisation of recombinant antibodies. BMC Biotechnol., 6, 46.
130. Schmiedl, A., Breitling, F., Winter, C.H., Queitsch, I., and Dübel, S. (2000) Effects of unpaired cysteines on yield, solubility and activity of different recombinant antibody constructs expressed in E. coli. J. Immunol. Methods, 242, 101-114.
131. Jäger, V., Büssow, K., Wagner, A., Weber, S., Hust, M., Frenzel, A., and Schirrmann, T. (2013) High level transient production of recombinant antibodies and antibody fusion proteins in HEK293 cells. BMC Biotechnol., 13, 52.
132. Pelat, T., Hust, M., Laffly, E., Condemine, F., Bottex, C., Vidal, D., Lefranc, M.-P., Dübel, S., and Thullier, P. (2007) High-affinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (LF) of Bacillus anthracis by inhibiting protective antigen-LF complex formation. Antimicrob. Agents Chemother., 51, 2758-2764.
133. Pelat, T., Hust, M., Hale, M., Lefranc, M.-P., Dübel, S., and Thullier, P. (2009) Isolation of a human-like antibody fragment (scFv) that neutralizes ricin biological activity. BMC Biotechnol., 9, 60.
134. Sun, L., Lu, X., Li, C., Wang, M., Liu, Q., Li, Z., Hu, X., Li, J., Liu, F., Li, Q., Belser, J.A., Hancock, K., Shu, Y., Katz, J.M., Liang, M., and Li, D. (2009) Generation, characterization and epitope mapping of two neutralizing and protective human recombinant antibodies against influenza A H5N1 viruses. PLoS One, 4, e5476.
135. Hust, M. and Dübel, S. (2004) Mating antibody phage display with proteomics. Trends Biotechnol., 22, 8-14.
136. Pershad, K., Pavlovic, J.D., Gräslund, S., Nilsson, P., Colwill, K., Karatt-Vellatt, A., Schofield, D.J., Dyson, M.R., Pawson, T., Kay, B.K., and McCafferty, J. (2010) Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display. Protein Eng. Des. Sel., 23, 279-288.
137. Colwill, K. and Gräslund, S. (2011) A roadmap to generate renewable protein binders to the human proteome. Nat. Methods, 8, 551-558.
138. Kirsch, M., Hülseweh, B., Nacke, C., Rülker, T., Schirrmann, T., Marschall, H.-J., Hust, M., and Dübel, S. (2008) Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV). BMC Biotechnol., 8, 66.
139. Mersmann, M., Meier, D., Mersmann, J., Helmsing, S., Nilsson, P., Gräslund, S., Structural Genomics Consortium, Colwill, K., Hust, M., Dübel, S., 2010. Towards proteome scale antibody selections using phage display. Nat. Biotechnol. 27, 118-128.
140. Schütte, M., Thullier, P., Pelat, T., Wezler, X., Rosenstock, P., Hinz, D., Kirsch, M.I., Hasenberg, M., Frank, R., Schirrmann, T., Gunzer, M., Hust, M., and Dübel, S. (2009) Identification of a putative Crf splice variant and generation of recombinant antibodies for the specific detection of Aspergillus fumigatus. PLoS One, 4, e6625.
141. Wezler, X., Hust, M., Helmsing, S., Schirrmann, T., and Dübel, S. (2012) Human antibodies targeting CD30+ lymphomas. Hum. Antibodies, 21, 13-28.
142. Zhang, C., Helmsing, S., Zagrebelsky, M., Schirrmann, T., Marschall, A.L.J., Schüngel, M., Korte, M., Hust, M., and Dübel, S. (2012) Suppression of p75 neurotrophin receptor surface expression with intrabodies influences Bcl-xL mRNA expression and neurite outgrowth in PC12 cells. PLoS One, 7, e30684.
143. Frenzel, A., Fröde, D., Meyer, T., Schirrmann, T., and Hust, M. (2012) Generating recombinant antibodies for research, diagnostics and therapy using phage display. Curr. Biotechol., 1, 33-41.
144. Glanville, J., Zhai, W., Berka, J., Telman, D., Huerta, G., Mehta, G.R., Ni, I., Mei, L., Sundar, P.D., Day, G.M.R., Cox, D., Rajpal, A., and Pons, J. (2009) Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire. Proc. Natl. Acad. Sci. U.S.A., 106, 20216-20221.
145. O'Connell, D., Becerril, B., Roy-Burman, A., Daws, M., and Marks, J.D. (2002) Phage versus phagemid libraries for generation of human monoclonal antibodies. J. Mol. Biol., 321, 49-56.
146. Jespers, L., Schon, O., Famm, K., and Winter, G. (2004) Aggregation-resistant domain antibodies selected on phage by heat denaturation. Nat. Biotechnol., 22, 1161-1165.
147. Hussack, G., Keklikian, A., Alsughayyir, J., Hanifi-Moghaddam, P., Arbabi-Ghahroudi, M., van Faassen, H., Hou, S.T., Sad, S., MacKenzie, R., and Tanha, J. (2012) A V(L) singledomain antibody library shows a highpropensity to yield non-aggregating binders. Protein Eng. Des. Sel., 25, 313-318.
148. Kwong, K.Y., Baskar, S., Zhang, H., Mackall, C.L., and Rader, C. (2008) Generation, affinity maturation, and characterization of a human antihuman NKG2D monoclonal antibody with dual antagonistic and agonistic activity. J. Mol. Biol., 384, 1143-1156.
149. Vaughan, T.J., Williams, A.J., Pritchard, K., Osbourn, J.K., Pope, A.R., Earnshaw, J.C., McCafferty, J., Hodits, R.A., Wilton, J., and Johnson, K.S. (1996) Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat. Biotechnol., 14, 309-314.
150. Philibert, P., Stoessel, A., Wang, W., Sibler, A.-P., Bec, N., Larroque, C., Saven, J.G., Courtete, J., Weiss, E., and Martineau, P. (2007) A focused antibody library for selecting scFvs expressed at high levels in the cytoplasm. BMC Biotechnol., 7, 81.
151. Azriel-Rosenfeld, R., Valensi, M., and Benhar, I. (2004) A human synthetic combinatorial library of arrayable single-chain antibodies based on shuffling in vivo formed CDRs into general framework regions. J. Mol. Biol., 335, 177-192.
152. Persson, M.A., Caothien, R.H., and Burton, D.R. (1991) Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning. Proc. Natl. Acad. Sci. U.S.A., 88, 2432-2436.
153. Barbas, C.F., Bain, J.D., Hoekstra, D.M., and Lerner, R.A. (1992) Semisynthetic combinatorial antibody libraries:a chemical solution to the diversity problem. Proc. Natl. Acad. Sci. U.S.A., 89, 4457-4461.
154. Barbas, C.F. III, Amberg, W., Simoncsits, A., Jones, T.M., and Lerner, R.A. (1993) Selection of human anti-hapten antibodies from semisynthetic libraries. Gene, 137, 57-62.
155. Zhu, Z., Dimitrov, A.S., Bossart, K.N., Crameri, G., Bishop, K.A., Choudhry, V., Mungall, B.A., Feng, Y.-R., Choudhary, A., Zhang, M.-Y., Feng, Y., Wang, L.-F., Xiao, X., Eaton, B.T., Broder, C.C., and Dimitrov, D.S. (2006) Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies. J. Virol., 80, 891-899.
156. Chen, W., Zhu, Z., Feng, Y., and Dimitrov, D.S. (2010) A large human domain antibody library combining heavy and light chain CDR3 diversity. Mol. Immunol., 47, 912-921.
157. Desiderio, A., Franconi, R., Lopez, M., Villani, M.E., Viti, F., Chiaraluce, R., Consalvi, V., Neri, D., and Benvenuto, E. (2001) A semi-synthetic repertoire of intrinsically stable antibody fragments derived from a single-framework scaffold. J. Mol. Biol., 310, 603-615.
158. Söderlind, E., Strandberg, L., Jirholt, P., Kobayashi, N., Alexeiva, V., Aberg, A.M., Nilsson, A., Jansson, B., Ohlin, M., Wingren, C., Danielsson, L., Carlsson, R., and Borrebaeck, C.A. (2000) Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat. Biotechnol., 18, 852-856.
159. Marks, J.D., Griffiths, A.D., Malmqvist, M., Clackson, T.P., Bye, J.M., and Winter, G. (1992) By-passing immunization:building high affinity human antibodies by chain shuffling. Biotechnology (N.Y.), 10, 779-783.
160. Villa, A., Lovato, V., Bujak, E., Wulhfard, S., Pasche, N., and Neri, D. (2011) A novel synthetic naïve human antibody library allows the isolation of antibodies against a new epitope of oncofetal fibronectin. MAbs, 3, 264-272.
161. Nissim, A., Hoogenboom, H.R., Tomlinson, I.M., Flynn, G., Midgley, C., Lane, D., and Winter, G. (1994) Antibody fragments from a "single pot" phage display library as immunochemical reagents. EMBO J., 13, 692-698.
162. De Kruif, J., Boel, E., and Logtenberg, T. (1995) Selection and application of human single chain Fv antibody fragments from a semi-synthetic phage antibody display library with designed CDR3 regions. J. Mol. Biol., 248, 97-105.
163. Christ, D., Famm, K., and Winter, G. (2007) Repertoires of aggregationresistant human antibody domains. Protein Eng. Des. Sel., 20, 413-416.
164. Fellouse, F.A., Li, B., Compaan, D.M., Peden, A.A., Hymowitz, S.G., and Sidhu, S.S. (2005) Molecular recognition by a binary code. J. Mol. Biol., 348, 1153-1162.
165. Dörsam, H., Rohrbach, P., Kürschner, T., Kipriyanov, S., Renner, S., Braunagel, M., Welschof, M., and Little, M. (1997) Antibodies to steroids from a small human naive IgM library. FEBS Lett., 414, 7-13.
166. Hayashi, N., Welschof, M., Zewe, M., Braunagel, M., Dübel, S., Breitling, F., and Little, M. (1994) Simultaneous mutagenesis of antibody CDR regions by overlap extension and PCR. Biotechniques, 17, 310, 312, 314-315.
167. Prassler, J., Thiel, S., Pracht, C., Polzer, A., Peters, S., Bauer, M., Nörenberg, S., Stark, Y., Kölln, J., Popp, A., Urlinger, S., and Enzelberger, M. (2011) HuCAL PLATINUM, a synthetic Fab library optimized for sequence diversity and superior performance in mammalian expression systems. J. Mol. Biol., 413, 261-278.
168. Rothe, C., Urlinger, S., Löhning, C., Prassler, J., Stark, Y., Jäger, U., Hubner, B., Bardroff, M., Pradel, I., Boss, M., Bittlingmaier, R., Bataa, T., Frisch, C., Brocks, B., Honegger, A., and Urban, M. (2008) The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of highaffinity antibodies. J. Mol. Biol., 376, 1182-1200.
169. Tiller, T., Schuster, I., Deppe, D., Siegers, K., Strohner, R., Herrmann, T., Berenguer, M., Poujol, D., Stehle, J., Stark, Y., Heßling, M., Daubert, D., Felderer, K., Kaden, S., Kölln, J., Enzelberger, M., and Urlinger, S. (2013) A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties. MAbs, 5.
170. Wu, T.T., Johnson, G., and Kabat, E.A. (1993) Length distribution of CDRH3 in antibodies. Proteins, 16, 1-7.
171. Johansen, L.K., Albrechtsen, B., Andersen, H.W., and Engberg, J. (1995) pFab60: a new, efficient vector for expression of antibody Fab fragments displayed on phage. Protein Eng., 8, 1063-1067.
172. Shirai, H., Kidera, A., and Nakamura, H. (1999) H3-rules: identification of CDR-H3 structures in antibodies. FEBS Lett., 455, 188-197.
173. Waterhouse, P., Griffiths, A.D., Johnson, K.S., and Winter, G. (1993) Combinatorial infection and in vivo recombination: a strategy for making large phage antibody repertoires. Nucleic Acids Res., 21, 2265-2266.
174. Bradbury, A., Sidhu, S., Dübel, S., and McCafferty, J. (2011) Beyond natural antibodies: the power of in vitro display technologies. Nature Biotechnol., 29, 245-254.
175. Dübel, S., Stoevesandt, O., Taussig, M.J., and Hust, M. (2010) Generating recombinant antibodies to the complete human proteome. Trends Biotechnol., 28, 333-339.
176. Hust, M., Toleikis, L., and Dübel, S. (2007) Handbook of Therapeutic Antibodies, Wiley-VCH Verlag GmbH, Weinheim, pp. 45-68.
177. Schirrmann, T., Meyer, T., Schütte, M., Frenzel, A., and Hust, M. (2011) Phage display for the generation of antibodies for proteome research, diagnostics and therapy. Molecules, 16, 412-426.