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Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1701))

Abstract

Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

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Acknowledgment

Work in our laboratory is supported by grants from the National Institutes of Health/National Cancer Institute (R01 CA171315, R01 CA118919, and R01 CA129491). NKL received fellowship support from Basic Science Research Program of the National Research Foundation of Korea (NRF) that is funded by the Ministry of Education, Science and Technology (2013R1A6A3A03060495).

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Correspondence to Bin Liu .

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Lee, NK., Bidlingmaier, S., Su, Y., Liu, B. (2018). Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes. In: Hust, M., Lim, T. (eds) Phage Display. Methods in Molecular Biology, vol 1701. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7447-4_4

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  • DOI: https://doi.org/10.1007/978-1-4939-7447-4_4

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7446-7

  • Online ISBN: 978-1-4939-7447-4

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