Abstract
Guided selection provides a powerful tool for humanization of the preexisting nonhuman antibodies as exemplified by HUMIRA, the world’s first human antibody approved. This chapter describes the sequential guided selection procedure in which mouse VL and VH domains are replaced sequentially with human VL and VH, respectively to derive completely human antibody. The detailed protocols for construction of phage-displayed antibody library, panning, screening, and characterization, are included to achieve successful selection of human antibody with similar characteristics to original mouse antibody.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Morrison SL, Johnson MJ, Herzenberg LA, Oi VT (1984) Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A 81:6851–6855
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G (1986) Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321:522–525
Winter G, Harris WJ (1993) Humanized antibodies. Immunol Today 14:243–246
Reichert JM (2001) Monoclonal antibodies in the clinic. Nat Biotechnol 19:819–822
Roguska MA, Pedersen JT, Keddy CA, Henry AH, Searle SJ, Lambert JM, Goldmacher VS, Blattler WA, Rees AR, Guild BC (1994) Humanization of murine monoclonal antibodies through variable domain resurfacing. Proc Natl Acad Sci U S A 91:969–973
Pendley C, Schantz A, Wagner C (2003) Immunogenicity of therapeutic monoclonal antibodies. Curr Opin Mol Ther 5:172–179
Jespers LS, Roberts A, Mahler SM, Winter G, Hoogenboom HR (1994) Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Bio/technology 12:899–903
Figini M, Marks JD, Winter G, Griffiths AD (1994) In vitro assembly of repertoires of antibody chains on the surface of phage by renaturation. J Mol Biol 239:68–78
Figini M, Obici L, Mezzanzanica D, Griffiths A, Colnaghi MI, Winter G, Canevari S (1998) Panning phage antibody libraries on cells: isolation of human Fab fragments against ovarian carcinoma using guided selection. Cancer Res 58:991–996
Watzka H, Pfizenmaier K, Moosmayer D (1998) Guided selection of antibody fragments specific for human interferon gamma receptor 1 from a human VH- and VL-gene repertoire. Immunotechnology 3:279–291
Beiboer SH, Reurs A, Roovers RC, Arends JW, Whitelegg NR, Rees AR, Hoogenboom HR (2000) Guided selection of a pan carcinoma specific antibody reveals similar binding characteristics yet structural divergence between the original murine antibody and its human equivalent. J Mol Biol 296:833–849
Schmidt A, Muller D, Mersmann M, Wuest T, Gerlach E, Garin-Chesa P, Rettig WJ, Pfizenmaier K, Moosmayer D (2001) Generation of human high-affinity antibodies specific for the fibroblast activation protein by guided selection. Eur J Biochem/FEBS 268:1730–1738
Zhang Q, Zhang SH, Su MQ, Bao GQ, Liu JY, Yi J, Shen JJ, Hao XK (2007) Guided selection of an anti-gamma-seminoprotein human Fab for antibody directed enzyme prodrug therapy of prostate cancer. Cancer Immunol Immunother 56:477–489
Wang Z, Wang Y, Li Z, Li J, Dong Z (2000) Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection. J Immunol Methods 241:171–184
Acknowledgements
This work was supported by a Medicinal Bioconvergence Research Center grant from the Ministry of Science and Technology of Korea.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Kim, S.J., Hong, H.J. (2012). Humanization by Guided Selections. In: Chames, P. (eds) Antibody Engineering. Methods in Molecular Biology, vol 907. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-974-7_14
Download citation
DOI: https://doi.org/10.1007/978-1-61779-974-7_14
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-973-0
Online ISBN: 978-1-61779-974-7
eBook Packages: Springer Protocols