Antibody Engineering: Humanization, Affinity Maturation, and Selection Techniques

Therapeutic Monoclonal Antibodies: From Bench to Clinic

Volumn , Issue , 2009, Pages 309-334

  Almagro, Juan C ^a   Strohl, William R ^a  

^a CENTOCOR INC   (United States)

Author keywords

Affinity maturation error prone PCR and DNA shuffling; Antibody engineering humanization, affinity maturation and selection techniques; Selection techniques

Indexed keywords

EID: 84891023097     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470485408.ch13     Document Type: Chapter

References (90)

1. Abhinandan, K.R., and A.C. Martin. 2007. Analyzing the "degree of humanness" of antibody sequences. J. Mol. Biol. 369:852-862.
2. Akamatsu, Y., K. Pakabunto, Z. Xu, Y. Zhang, and N. Tsurushita. 2007. Whole IgG surface display on mammalian cells: Application to isolation of neutralizing chicken monoclonal anti-IL-12 antibodies. J. Immunol. Methods 327:40-52.
3. Al-Lazikani, B., A.M. Lesk, and C. Chothia. 1997. Standard conformations for the canonical structures of immunoglobulins. J. Mol. Biol. 273:927-948.
4. Almagro, J.C., and J. Fransson. 2008. Humanization of antibodies. Front. Biosci. 13:1619-1633.
5. Almagro, J.C., V. Quintero-Hernandez, M. Ortiz-Leon, A. Velandia, S.L. Smith, and B. Becerril. 2006. Design and validation of a synthetic VH repertoire with tailored diversity for protein recognition. J. Mol. Recognit. 19:413-422.
6. Amzel, L.M., and R.J. Poljak. 1979. Three-dimensional structure of immunoglobulins. Annu. Rev. Biochem. 48:961-997.
7. Baca, M., L.G. Presta, S.J. O'Connor, and J.A. Wells. 1997. Antibody humanization using monovalent phage display. J. Biol. Chem. 272:10678-10684.
8. Biles, B.D., and B.A. Connolly. 2004. Low-fidelity Pyrococcus furiosus DNA polymerase mutants useful in error-prone PCR. Nucleic Acids Res. 32:e176.
9. Blaise, L., A. Wehnert, M.P.G. Steukers, T. van den Beucken, H.R. Hoogenboom, and S.E. Hufton. 2004. Construction and diversification of yeast cell surface displayed libraries by yeast mating: Application to the affinity maturation of Fab antibody fragments. Gene 342:211-218.
10. Boder, E.T., and K.D. Wittrup. 2000. Yeast surface display for directed evolution of protein expression, affinity, and stability. Methods Enzymol. 328:430-444.
11. Boder, E.T., K.S. Midelfort, and K.D. Wittrup. 2000. Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc. Natl. Acad. Sci. USA 97:10701-10705.
12. Bruccoleri, R.E., and M. Karplus. 1987. Prediction of the folding of short polypeptide segments by uniform conformational sampling. Biopolymers 26:137-168.
13. Chodorge, M., L. Fourage, G. Ravot, L. Jermutus, and R. Minter. 2008. In vitro DNArecombination by L-shuffling during ribosome display affinity maturation of an anti-Fas antibody increases the population of improved variants. Protein Eng. Des. Sel. 21:343-351.
14. Chothia, C., and A.M. Lesk. 1987. Canonical structures for the hypervariable regions of immunoglobulins. J. Mol. Biol. 196:901-917.
15. Christ, D., K. Famm, and G. Winter. 2007. Repertoires of aggregation-resistant human antibody domains. Protein Eng. Des. Sel. 20:413-416.
16. Corbett, S.J., I.M. Tomlinson, E.L. Sonnhammer, D. Buck, and G. Winter. 1997. Sequence of the human immunoglobulin diversity (D) segment locus: A systematic analysis provides no evidence for the use of DIR segments, inverted D segments, "minor" D segments or D-D recombination. J. Mol. Biol. 270:587-597.
17. Daugherty, P.S., G. Chen, B.L. Iverson, and G. Georgiou. 2000. Quantitative analysis of the effect of the mutation frequency on the affinity maturation of single chain Fv antibodies. Proc. Natl. Acad. Sci. USA 97:2029-2034.
18. Daugherty, B.L., G.E. Mark III, and E.A. Padlan. 2004. Method for reducing the immunogenicity of antibody variable domains. 45 pp. US 6,797,492 B2.
19. Delagrave, S., J. Catalan, C. Sweet, G. Drabik, A. Henry, A. Rees, T.P. Monath, and F. Guirakhoo. 1999. Effects of humanization by variable domain resurfacing on the antiviral activity of a single chain antibody against respiratory syncytial virus. Protein Eng. 12:357-362.
20. De Pascalis, R., M. Iwahashi, M. Tamura, E.A. Padlan, N.R. Gonzales, A.D. Santos, M. Giuliano, P. Schuck, J. Schlom, and S.V. Kashmiri. 2002. Grafting of "abbreviated" complementarity-determining regions containing specificity-determining residues essential for ligand contact to engineer a less immunogenic humanized monoclonal antibody. J. Immunol. 169:3076-3084.
21. Dufner, P., L. Jermatus, and R.R. Minter. 2006. Harnessing phage and ribosome display for antibody optimization. Trends Biotechnol. 24:523-529.
22. Famm, K., L. Hansen, D. Christ, and G. Winters. 2008. Thermodynamically stable aggregation-resistant antibody domains through directed evolution. J. Mol. Biol. 376:926-931.
23. Foote, J., and H.N. Eisen. 1995. Kinetic and affinity limits on antibodies produced during immune responses. Proc. Natl. Acad. Sci. USA 92:1254-1256.
24. Foote, J., and G. Winter. 1992. Antibody framework residues affecting the conformation of the hypervariable loops. J. Mol. Biol. 224:487-499.
25. Fukuda, I., K. Kojoh, N. Tabata, N. Doi, H. Takashima, E. Miyamoto-Sato, and H. Yanagawa. 2006. In vitro evolution of single-chain antibodies using mRNA display. Nucleic Acids Res. 34:e127, 1-8.
26. Gai, S.A., and K.D. Wittrup. 2007. Yeast surface display for protein engineering and characterization. Curr. Opin. Struct. Biol. 17:467-473.
27. Gao, C., S. Mao, C.H. Lo, P. Wirsching, R.A. Lerner, and K.D. Janda. 1999. Making artificial antibodies: A format for phage display of combinatorial heterodimeric arrays. Proc. Natl. Acad. Sci. USA 96:6025-6030.
28. Gonzales, N.R., E.A. Padlan, R. De Pascalis, P. Schuck, J. Schlom, and S.V. Kashmiri. 2004. SDR grafting of a murine antibody using multiple human germline templates to minimize its immunogenicity. Mol. Immunol. 41:863-872.
29. Graff, C.P., K. Chester, R. Begent, and K.D. Wittrup. 2004. Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation time at 37 degrees C. Protein Eng. Des. Sci. 17:293-304.
30. Groves, M., S. Lane, J. Douthwaite, D. Lowne, D.G. Rees, B. Edwards, and R.H. Jackson. 2006. Affinity maturation of phage display antibody populations using ribosome display. J. Immunol. Methods 313:129-139.
31. Harvey, B.R., G. Georgiou, A. Hayhurst, K.J. Jeong, B.L. Iverson, and G.K. Rogers. 2004. Anchored periplasmic expression, a versatile technology for the isolation of high-affinity antibodies from Escherichia coli-expressed libraries. Proc. Natl. Acad. Sci USA 101:9193-9198.
32. He, M., and F. Khan. 2005. Ribosome display: Next generation display technologies for production of antibodies in vitro. Expert Rev. Proteomics 2:421-430.
33. Ho, M., S. Nagata, and I. Pastan. 2006. Isolation of anti-CD22 Fv with high affinity by Fv display on human cells. Proc. Natl. Acad. Sci. USA 103:9637-9642.
34. Hoet, R.M., E.H. Cohen, R.B. Kent, K. Rookey, S. Schoonbroodt, S. Hogan, L. Rem, N. Frans, M. Daukandt, H. Pieters, R. van Hegelsom, N.C. Neer, H.G. Nastri, I.J. Rondon, J.A. Leeds, S.E. Hufton, L. Huang, I. Kashin, M. Devlin, G. Kuang, M. Steukers, M. Viswanathan, A.E. Nixon, D.J. Sexton, H.R. Hoogenboom, and R.C. Ladner. 2005. Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nature Biotechnol. 23:344-348.
35. Hoogenboom, H.R. 2005. Selecting and screening recombinant antibody libraries. Nature Biotechnol. 23:1105-1116.
36. Hu, W.G., D. Chau, J. Wu, S. Jager, and L.P. Nagata. 2007. Humanization and mammalian expression of a murine monoclonal antibody against Venezuelan equine encephalitis virus. Vaccine 25:3210-3214.
37. Hwang, W.Y., and J. Foote. 2005. Immunogenicity of engineered antibodies. Methods 36:3-10.
38. Hwang, W.Y., J.C. Almagro, T.N. Buss, P. Tan, and J. Foote. 2005. Use of human germline genes in a CDR homology-based approach to CDR grafting. Methods 36:35-42.
39. Jespers, L.S., A. Roberts, S.M. Mahler, G. Winter, and H.R. Hoogenboom. 1994. Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Biotechnology (NY). 12:899-903.
40. Jespers, L., O. Schon, K. Famm, and G. Winter. 2004. Aggregation-resistant domain antibodies selected on phage by heat denaturation. Nature Biotechnol. 22:1161-1165.
41. Jones, P.T., P.H. Dear, J. Foote, M.S. Neuberger, and G. Winter. 1986. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321:522-525.
42. Kashmiri, S.V., R. De Pascalis, N.R. Gonzales, and J. Schlom. 2005. SDR grafting: A new approach to antibody humanization. Methods 36:25-34.
43. Kimball, J.A., D.J. Norman, C.F. Shield, T.J. Schroeder, P. Lisi, M. Garovoy, J.B. O'Connell, F. Stuart, S.V. McDiarmid, and W. Wall. 1995. The OKT3 antibody response study: A multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation. Transpl. Immunol. 3(3):212-221.
44. Knappik A, L. Ge, A. Honegger, P. Pack, M. Fischer, G. Wellnhofer, A. Hoess, J. Wolle, A. Pluckthun, and B. Virnekas. 2000. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J. Mol. Biol. 296:57-86.
45. Koren, E., L.A. Zuckerman, and A.R. Mire-Sluis. 2002. Immune responses to therapeutic proteins in humans: Clinical significance, assessment and prodiction. Curr. Pharmaceut. Biotechnol. 3:349-368.
46. Kuepper, M.B., M. Huhn, H. Spiegel, J.K. Ma, S. Barth, R. Fischer, and R. Finnern. 2005. Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach. BMC Biotechnol. 5(4):1-12.
47. Lazar, G.A., J.R. Desjarlais, J. Jacinto, S. Karki, and P.W. Hammond. 2007. A molecular immunology approach to antibody humanization and functional optimization. Mol. Immunol. 44:1986-1998.
48. Lee, C.V., W.C. Liang, M.S. Dennis, C. Eigenbrot, S.S. Sidhu, and G. Fuh. 2004. High-affinity human antibodies from phage-displayed synthetic Fab libraries with a single framework scaffold. J. Mol. Biol. 340:1073-1093.
49. Lipovsek, D., and A. Pluckthun. 2004. In-vitro protein evolution by ribosome display and mRNA display. J. Immunol. Methods 290:51-67.
50. Lippow, S.M., and B. Tidor. 2007. Progress in computational protein design. Curr. Opin. Biotechnol. 18:305-311.
51. Lippow, S.M., K.D. Wittrup, and B. Tidor. 2007. Computational design of antibody-affinity improvement beyond in vivo maturation. Nature Biotechnol. 25:1171-1176.
52. Luginbuhl, B., Z. Kanyo, R.M. Jones, R.J. Fletterick, S.B. Prusiner, F.E. Cohen, R.A. Williamson, D.R. Burton, and A. Pluckthun. 2006. Directed evolution of an anti-prion protein scFv fragment to an affinity of 1 pM and its structural interpretation. J. Mol. Biol. 363:75-97.
53. Marks, J.D., H.R. Hoogenboom, T.P. Bonnert, J. McCafferty, A.D. Griffiths, and G. Winter. 1991. By-passing immunization. Human antibodies from V-gene libraries displayed on phage. J. Mol. Biol. 222:581-597.
54. McCafferty, J., A.D. Griffiths, G. Winter, and D.J. Chiswell. 1990. Phage antibodies: Filamentous phage displaying antibody variable domains. Nature 348:552-554.
55. Mukovosov, I., T. Sabljic, G. Hortelano, and F. Ofosu. 2008. Factors that contribute to the immunogenicity of therapeutic recombinant human proteins. Thromb. Haemost. 99:874-882.
56. Neylon, C. 2004. Chemical and biochemical strategies for the randomization of protein encoding DNA sequences: library construction methods for directed evolution. Nucl. Acids. Res. 32:1448-1459.
57. Osbourn, J., M. Groves, and T. Vaughan. 2005. From rodent reagents to human therapeutics using antibody guided selection. Methods 36:61-68.
58. Padlan, E.A., C. Abergel, and J.P. Tipper. 1995. Identification of specificity-determining residues in antibodies. FASEB J. 9:133-139.
59. Pendley, C., A. Schantz, and C. Wagner. 2003. Immunogenicity of therapeutic monoclonal antibodies. Curr. Opin. Mol. Therap. 5:172-179.
60. Queen, C., W.P. Schneider, H.E. Selick, P.W. Payne, N.F. Landolfi, J.F. Duncan, N.M. Avdalovic, M. Levitt, R.P. Junghans, and T.A. Waldmann. 1989. A humanized antibody that binds to the interleukin 2 receptor. Proc. Natl. Acad. Sci. USA 86, 10029-10033.
61. Ramirez-Benitez, M.C., and J.C. Almagro. 2001. Analysis of antibodies of known structure suggests a lack of correspondence between the residues in contact with the antigen and those modified by somatic hypermutation. Proteins 45:199-206.
62. Rathanaswami, P., S. Roalstad, L. Roskos, Q.J. Su, S. Lackie, and J. Babcook. 2005. Demonstration of an in vivo generated sub-picomolar affinity fully human monoclonal antibody to interleukin-8. Biochem. Biophys. Res. Commun. 334:1004-1013.
63. Riley, S. 2006. In The Future of Monoclonal Antibodies. Business Insight Ltd., London.
64. Roguska, M.A., J.T. Pedersen, A.H. Henry, S.M.J. Searle, C. M. Roja, B. Avery, M. Hoffee, S. Cook, J.M. Lambert, W.A. Blaettler, A.R. Rees, and B.C. Guild. 1994. A comparison of two murine monoclonal antibodies humanized by CDR-grafting and variable domain resurfacing. Protein Eng. 9:895-904.
65. Roguska, M.A., J.T. Pedersen, C.A. Keddy, A.H. Henry, S.J. Searle, J.M. Lambert, V.S. Goldmacher, W.A. Blaettler, A.R. Rees, and B.C. Guild. 1994. Humanization of murine monoclonal antibodies through variable domain resurfacing. Proc. Natl. Acad. Sci. USA 91:969-973.
66. Schier, R., A. McCall, G.P. Adams, K.W. Marshall, H. Merritt, M. Yim, R.S. Crawford, L.M. Weiner, C. Marks, and J.D. Marks. 1996. Isolation of picomolar affinity anti-c-erbB-2 single-chain Fv by molecular evolution of the complementarity determining regions in the center of the antibody binding site. J. Mol. Biol. 263:551-567.
67. Schwartz, M., P. Boettgen, Y. Takada, F. Le Gall, S. Knackmuss, N. Bassler, C. Buettner, M. Little, C. Bode, and K. Peter. 2004. Single-chain antibodies for the conformation-specific blockade of activated platelet integrin alpha-II beta-3 designed by subtractive selection from naive human phage libraries. FASEB J. 18:1704-1706.
68. Sidhu, S.S., and F.A. Fellouse. 2006. Synthetic therapeutic antibodies. Nature Chem. Biol. 2:682-688.
69. Smith, G.P. 1985. Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. Science 228:1315-1317.
70. Soderlind, E., L. Strandberg, P. Jirholt, N. Kobayashi, V. Alexeiva, A.M. Aberg, A. Nilsson, B. Jansson, M. Ohlin, C. Wingren, L. Danielsson, R. Carlsson, and C.A. Borrebaeck. 2000. Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nature Biotechnol. 18:852-856.
71. Staelens, S., J. Desmet, T.H. Ngo, S. Vauterin, I. Pareyn, P. Barbeaux, I. Van Rompaey, J.-M. Stassen, H. Deckmyn, and K. Vanhoorelbeke. 2006. Humanization by variable domain resurfacing and grafting on a human IgG4, using a new approach for determination of non-human like surface accessible framework residues based on homology modeling of variable domains. Mol. Immunol. 43:1243-1257.
72. Steinberger, P., J.K. Sutton, C. Rader, M. Elia, and C.F. Barbas. 2000. Generation and characterization of arecom-binant human CCR5-specific antibody. A phage display approach rabbit antibody humanization. J. Biol. Chem. 275:36073-36078.
73. Stemmer, W.P. 1994. DNA shuffling by random fragmentation and reassembly: In vitro recombination for molecular evolution. Proc. Natl. Acad. Sci. USA 91:10747-10751.
74. Tamura, M., D.E. Milenic, M. Iwahashi, E. Padlan, J. Schlom, and S.V. Kashmiri. 2000. Structural correlates of an anticarcinoma antibody: Identification of specificity-determining residues (SDRs) and development of a minimally immunogenic antibody variant by retention of SDRs only. J. Immunol. 164:1432-1441.
75. Tan, P., D.A. Mitchell, T.N. Buss, M.A. Holmes, C. Anasetti, and J. Foote. 2002. "Superhumanized" antibodies: Reduction of immunogenic potential by complementarity-determining region grafting with human germline sequences-application to an anti-CD28. J. Immunol. 169:1119-11125.
76. Thom, G., A.C. Cockroft, A.G. Buchanan, C.J. Candotti, E.S. Cohen, D. Lowne, P. Monk, C.P. Shorrock-Hart, L. Jermatus, and R.R. Minter. 2006. Probing a protein-protein interaction by in vitro evolution. Proc. Natl. Acad. Sci. USA 103:7619-7624.
77. Tonegawa, S. 1983. Somatic generation of antibody diversity. Nature 302:575-581.
78. Tomlinson, I.M., G. Walter, P.T. Jones, P.H. Dear, E.L. Sonnhammer, and G. Winter. 1996. The imprint of somatic hypermutation on the repertoire of human germline V genes. J. Mol. Biol. 256:813-817.
79. Van den Beucken, T., H. Pieters, M. Steukers, M. van der Vaart, R.C. Ladner, H.R. Hoogenboom, and S.E. Hufton. 2003. Affinity maturation of Fab antibody fragments by fluorescent-activated cell sorting of yeast-displayed libraries. FEBS Lett. 546:288-294.
80. Wang, Z., Y. Wang, Z. Li, J. Li, and Z. Dong. 2000. Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection. J. Immunol. Methods 241:171-184.
81. Wark, K.L., and P.J. Hudson. 1996. Latest technologies for the enhancement of antibody affinity. Adv. Drug Deliv. Rev. 58:657-670.
82. Watzka, H., K. Pfizenmaier, and D. Moosmayer. 1998. Guided selection of antibody fragments specific for human interferon g receptor 1 from a human VH-and VL-gene repertoire. Immunotechnology 3:279-291.
83. Weaver-Feldhaus, J.M., J. Lou, J.R. Coleman, R.W. Siegel, J.D. Marks, and M.J. Feldhaus. 2004. Yeast mating for combinatorial Fab library generation and surface display. FEBS Lett. 564:24-34.
84. Wedemayer, G.J., P.A. Patten, L.H. Wang, P.G. Schultz, and R.C. Stevens. 1997. Structural insights into the evolution of an antibody combining site. Science 276:1665-1669.
85. Wu., H., D.S. Pfarr, Y. Tang, L.L. An, N.K. Patel, J.D. Watkins, W.D. Huse, P.A. Kiener, and J.F. Young. 2005. Ultra-potent antibodies against respiratory syncytial virus: effects of binding kinetics and binding valence on viral neutralization. J. Mol. Biol. 350:126-144.
86. Wu, T.T., and E.A. Kabat. 1970. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J. Exp. Med. 132:211-250.
87. Yan, X., and Z. Xu. 2006. Ribosome-display technology: Applications for directed evolution of functional proteins. Drug Discovery Today 11:911-916.
88. Yang, W.P., K. Green, S. Pinz-Sweeney, A.T. Briones, D.R. Burton, and C.F. Barbas III. 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.
89. Zahnd, C., P. Amstutz, and A. Pluckthun. 2007. Ribosome display: Selecting and evolving proteins in vitro that specifically bind to a target. Nature Methods 4:269-279.
90. Zahnd, C., S. Spinelli, B. Luginbuhl, P. Amstutz, C. Cambillau, and A. Pluckthun. 2004. Directed in vitro evolution and crystallographic analysis of a peptide-binding single chain antibody fragment (scFv) with low picomolar affinity. J. Biol. Chem. 279:18870-18877.