In vitro evolution of antibodies inspired by in vivo evolution
Persson, Helena ; Kirik, Ufuk LU ; Thörnqvist, Linnea LU ; Greiff, Lennart LU ; Levander, Fredrik LU and Ohlin, Mats LU
(2018)
In Frontiers in Immunology
9(JUN).
- Abstract
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... (More)
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.
(Less)
- author
- Persson, Helena
; Kirik, Ufuk
LU
; Thörnqvist, Linnea
LU
; Greiff, Lennart
LU
; Levander, Fredrik
LU
and Ohlin, Mats
LU
- organization
- publishing date
- 2018-06-21
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Affinity maturation, Antibody, Antibody therapeutics, Developability, Evolution, Humanization, Immunoglobulin germline gene, Somatic hypermutation
- in
- Frontiers in Immunology
- volume
- 9
- issue
- JUN
- article number
- 1391
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85048823650
- pmid:29977238
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2018.01391
- language
- English
- LU publication?
- yes
- id
- e9fe7385-7498-4367-902e-0fec76ce6975
- date added to LUP
- 2018-07-05 10:56:59
- date last changed
- 2024-04-01 07:54:52
@article{e9fe7385-7498-4367-902e-0fec76ce6975,
abstract = {{<p>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.</p>}},
author = {{Persson, Helena and Kirik, Ufuk and Thörnqvist, Linnea and Greiff, Lennart and Levander, Fredrik and Ohlin, Mats}},
issn = {{1664-3224}},
keywords = {{Affinity maturation; Antibody; Antibody therapeutics; Developability; Evolution; Humanization; Immunoglobulin germline gene; Somatic hypermutation}},
language = {{eng}},
month = {{06}},
number = {{JUN}},
publisher = {{Frontiers Media S. A.}},
series = {{Frontiers in Immunology}},
title = {{In vitro evolution of antibodies inspired by in vivo evolution}},
url = {{http://dx.doi.org/10.3389/fimmu.2018.01391}},
doi = {{10.3389/fimmu.2018.01391}},
volume = {{9}},
year = {{2018}},
}