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4 - Antibody Libraries from Naïve V Gene Sources

from PART II - GENERATION AND SCREENING OF ANTIBODY LIBRARIES

Published online by Cambridge University Press:  15 December 2009

By
Gerald Beste  and
David Lowe
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

Recombinant human antibody repertoires are now used routinely for the identification of individual antibodies with defined specificities to any conceivable antigen. The generation of large libraries (>1010) has been reported from many commercial and academic laboratories, along with a growing number of examples of isolated antibodies in clinical development for a range of therapeutic applications. Our laboratory has constructed nonimmunized libraries of human scFv antibody fragments with a combined size of >1011 transformants that have been used for more than ten years to successfully isolate antibodies suitable for clinical development.

LIBRARY DESIGN CONSIDERATIONS

Natural Antibody Diversity

The common aim of all nonimmunized recombinant antibody libraries is to mirror the immune system's ability to provide binding specificity to any antigen. For naïve human antibody libraries this is achieved by capturing the full spectrum of antibody sequences available from the human B cell repertoire.

The primary repertoire of variable heavy and light chain DNA sequences is generated by the recombination of V, J, and in case of the heavy chain, also D gene segments, which can recombine to give 7,650 (16,218 considering the use of multiple reading frames for the D segments) different VH and 324 different VL sequences (Corbett et al., 1997; Nossal, 2003).

Type
Chapter
Information
Recombinant Antibodies for Immunotherapy , pp. 55 - 65
Publisher: Cambridge University Press
Print publication year: 2009

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