Antibody Gene Libraries

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (28 February 2015) | Viewed by 18045

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Special Issue Information

Dear Colleagues,

Since the first publication by Kohler and Milstein on the production of mouse monoclonal antibodies (mAbs) by hybridoma technology, mAbs have had a profound impact on medicine and have become a major part of treatments for various ailments, including transplantation, oncology, autoimmune, cardiovascular, and infectious diseases. While murine, chimeric, and humanized mAbs have been approved for treatment, future opportunities rely on the development of fully human antibodies for clinical applications. Remarkable progress in this direction has been made following the development of antibody gene libraries, namely the display technologies that enable the engineering of antibodies with modified properties (e.g., molecular size, affinity, specificity, and valency).

In this Special Issue of Antibodies, gene libraries will highlight advances in the display technologies that can be sources of fully human antibodies engineered for optimal clinical performance. The issue will review the various antibody displayed formats (e.g., phage, yeast, bacteria or cells). Alternative libraries that are not based on an antibody backubone will also be described. Examples of clinical applications will be reviewed.

Dr. Ahuva Nissim
Guest Editor

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Keywords

  • phage display
  • yeast display
  • cell display
  • bacterial display
  • scFv, domain
  • alternative backbone libraries

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Published Papers (2 papers)

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Research

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Article
Purpose-Oriented Antibody Libraries Incorporating Tailored CDR3 Sequences
by Pauline Bonvin, Sophie Venet, Marie Kosco-Vilbois and Nicolas Fischer
Antibodies 2015, 4(2), 103-122; https://doi.org/10.3390/antib4020103 - 20 May 2015
Cited by 5 | Viewed by 9330
Abstract
The development of in vitro antibody selection technologies has allowed overcoming some limitations inherent to the hybridoma technology. In most cases, large repertoires of antibody genes have been assembled to create highly diversified libraries allowing the isolation of antibodies recognizing virtually any antigen. [...] Read more.
The development of in vitro antibody selection technologies has allowed overcoming some limitations inherent to the hybridoma technology. In most cases, large repertoires of antibody genes have been assembled to create highly diversified libraries allowing the isolation of antibodies recognizing virtually any antigen. However, these universal libraries might not allow the isolation of antibodies with specific structural properties or particular amino acid contents that are rarely found in natural repertoires. Purpose-oriented libraries specially designed to incorporate desired characteristics have been successfully used. However, the workload required for library construction has limited the attractiveness of this approach compared to the use of large universal libraries. We have developed an approach to capture synthetic or natural diversity into the complementarity determining regions 3 (CDR3) of human antibody repertoires using Type IIS restriction enzymes. In this way, we generated several libraries either biased in amino acid content or towards long CDRH3 loops. The latter were successfully used to identify antibodies inhibiting the enzymatic activity of horseradish peroxidase, whereas libraries enriched in histidines allowed for the isolation of antibodies binding to human Fc in a pH-dependent manner. These libraries indicate that tailored diversification of CDR3 is sufficient to generate purpose-oriented libraries and isolate antibodies with uncommon properties. Full article
(This article belongs to the Special Issue Antibody Gene Libraries)
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Article
A Monoclonal Antibody to Human DLK1 Reveals Differential Expression in Cancer and Absence in Healthy Tissues
by Emil Bujak, Danilo Ritz and Dario Neri
Antibodies 2015, 4(2), 71-87; https://doi.org/10.3390/antib4020071 - 16 Apr 2015
Cited by 4 | Viewed by 8224
Abstract
There is considerable interest in the characterization of novel tumor-associated antigens that lend themselves to antibody-mediated pharmacodelivery strategies. Delta-like 1 homolog protein (DLK1), which exists both as transmembrane protein and in soluble form, shows a restricted pattern of expression in healthy organs, while [...] Read more.
There is considerable interest in the characterization of novel tumor-associated antigens that lend themselves to antibody-mediated pharmacodelivery strategies. Delta-like 1 homolog protein (DLK1), which exists both as transmembrane protein and in soluble form, shows a restricted pattern of expression in healthy organs, while being overexpressed in some tumors. We have generated a human antibody specific to DLK1 using phage display technology. This reagent was used for a comprehensive characterization of DLK1 expression in freshly frozen sections of normal human adult tissues and of xenografted human tumors. DLK1 was virtually undetectable in most organs, except for placenta which was weakly positive. By contrast, DLK1 exhibited a moderate-to-strong expression in 8/9 tumor types tested. Our analysis shed light on previous conflicting reports on DLK1 expression in health and disease. The study suggests that DLK1 may be considered as a target for antibody-mediated pharmacodelivery strategies, in view of the protein’s limited expression in normal tissues and its abundance in the interstitium of neoplastic lesions. Full article
(This article belongs to the Special Issue Antibody Gene Libraries)
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