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In Vitro Evolution of Antibodies Inspired by In Vivo Evolution
KTH, Centres, Science for Life Laboratory, SciLifeLab.
Lund Univ, Dept Immunotechnol, Lund, Sweden.;Univ Copenhagen, Novo Nordisk Fdn, Ctr Prot Res, Copenhagen, Denmark..
Lund Univ, Dept Immunotechnol, Lund, Sweden..
Lund Univ, Dept Clin Sci, Lund, Sweden.;Skane Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Lund, Sweden..
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 1391Article in journal (Refereed) Published
Abstract [en]

In vitro generation of antibodies often requires variable domain sequence evolution to adapt the protein in terms of affinity, specificity, or developability. Such antibodies, including those that are of interest for clinical development, may have their origins in a diversity of immunoglobulin germline genes. Others and we have previously shown that antibodies of different origins tend to evolve along different, preferred trajectories. Apart from substitutions within the complementary determining regions, evolution may also, in a germline gene-origin-defined manner, be focused to residues in the framework regions, and even to residues within the protein core, in many instances at a substantial distance from the antibody's antigen-binding site. Examples of such germline origin-defined patterns of evolution are described. We propose that germline gene-preferred substitution patterns offer attractive alternatives that should be considered in efforts to evolve antibodies intended for therapeutic use with respect to appropriate affinity, specificity, and product developability. We also hypothesize that such germline gene-origin-defined in vitro evolution hold potential to result in products with limited immunogenicity, as similarly evolved antibodies will be parts of conventional, in vivo-generated antibody responses and thus are likely to have been seen by the immune system in the past.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018. Vol. 9, article id 1391
Keywords [en]
affinity maturation, antibody, antibody therapeutics, developability, evolution, humanization, immunoglobulin germline gene, somatic hypermutation
National Category
Immunology
Identifiers
URN: urn:nbn:se:kth:diva-240226DOI: 10.3389/fimmu.2018.01391ISI: 000435772000001PubMedID: 29977238Scopus ID: 2-s2.0-85048823650OAI: oai:DiVA.org:kth-240226DiVA, id: diva2:1270683
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20181214

Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2018-12-14Bibliographically approved

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Persson, Helena

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