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In Vitro Evolution ...
In Vitro Evolution of Antibodies Inspired by In Vivo Evolution
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- Persson, Helena (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Science for Life Laboratory (SciLifeLab)
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- Kirik, Ufuk (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Thörnqvist, Linnea (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Greiff, Lennart (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Levander, Fredrik (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Ohlin, Mats (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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(creator_code:org_t)
- 2018-06-21
- 2018
- English.
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 9
- Related links:
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- affinity maturation
- antibody
- antibody therapeutics
- developability
- evolution
- humanization
- immunoglobulin germline gene
- somatic hypermutation
- Affinity maturation
- Antibody
- Antibody therapeutics
- Developability
- Evolution
- Humanization
- Immunoglobulin germline gene
- Somatic hypermutation
Publication and Content Type
- ref (subject category)
- art (subject category)
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