Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery
Heavy chain-only antibodies have found many applications where conventional heavy-light heterodimeric antibodies are not favorable. Heavy chain-only antibodies with their single antigen-binding domain offer the advantage of a smaller size and higher stability relative to conventional antibodies, and...
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| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2435476 |
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| author | Christine N. Vuong Kevin M. Reynolds Gerry S. Rivera Baisen Zeng Zahra Karimpourkalou Manith Norng Yulei Zhang Robayet Chowdhury Darlene Pedersen Melissa Pantoja Ellen Collarini Swetha Garimalla Shelley Izquierdo Eric G. Vajda Brett Antonio Devendra B. Srivastava Marie-Cecile van de Lavoir Yasmina Abdiche William Harriman Philip A. Leighton |
| author_facet | Christine N. Vuong Kevin M. Reynolds Gerry S. Rivera Baisen Zeng Zahra Karimpourkalou Manith Norng Yulei Zhang Robayet Chowdhury Darlene Pedersen Melissa Pantoja Ellen Collarini Swetha Garimalla Shelley Izquierdo Eric G. Vajda Brett Antonio Devendra B. Srivastava Marie-Cecile van de Lavoir Yasmina Abdiche William Harriman Philip A. Leighton |
| author_sort | Christine N. Vuong |
| collection | DOAJ |
| description | Heavy chain-only antibodies have found many applications where conventional heavy-light heterodimeric antibodies are not favorable. Heavy chain-only antibodies with their single antigen-binding domain offer the advantage of a smaller size and higher stability relative to conventional antibodies, and thus, the potential for novel targeting modalities. Domain antibodies have commonly been sourced from camelids with ex-vivo humanization or transgenic rodents expressing heavy chains without light chains, but these host species are all mammalian, limiting their capacity to elicit robust immune responses to conserved mammalian targets. We have developed transgenic chickens expressing heavy chain-only antibodies with a human variable region to combine the superior target recognition advantages of a divergent, non-mammalian host with the ability to discover single-domain binders. These birds produce robust immune responses, consisting of antigen-specific antibodies targeting diverse epitopes with a range of affinities. Biophysical attributes are favorable, with good developability profiles and low predicted immunogenicity. |
| format | Article |
| id | doaj-art-e1ab1681fce44c14a4eb463c71ee1174 |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-e1ab1681fce44c14a4eb463c71ee11742025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2435476Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discoveryChristine N. Vuong0Kevin M. Reynolds1Gerry S. Rivera2Baisen Zeng3Zahra Karimpourkalou4Manith Norng5Yulei Zhang6Robayet Chowdhury7Darlene Pedersen8Melissa Pantoja9Ellen Collarini10Swetha Garimalla11Shelley Izquierdo12Eric G. Vajda13Brett Antonio14Devendra B. Srivastava15Marie-Cecile van de Lavoir16Yasmina Abdiche17William Harriman18Philip A. Leighton19OmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAOmniAb, Inc, Emeryville, CA, USAHeavy chain-only antibodies have found many applications where conventional heavy-light heterodimeric antibodies are not favorable. Heavy chain-only antibodies with their single antigen-binding domain offer the advantage of a smaller size and higher stability relative to conventional antibodies, and thus, the potential for novel targeting modalities. Domain antibodies have commonly been sourced from camelids with ex-vivo humanization or transgenic rodents expressing heavy chains without light chains, but these host species are all mammalian, limiting their capacity to elicit robust immune responses to conserved mammalian targets. We have developed transgenic chickens expressing heavy chain-only antibodies with a human variable region to combine the superior target recognition advantages of a divergent, non-mammalian host with the ability to discover single-domain binders. These birds produce robust immune responses, consisting of antigen-specific antibodies targeting diverse epitopes with a range of affinities. Biophysical attributes are favorable, with good developability profiles and low predicted immunogenicity.https://www.tandfonline.com/doi/10.1080/19420862.2024.2435476Heavy chain-onlysdabsingle-domain antibodytransgenic chickenVHH |
| spellingShingle | Christine N. Vuong Kevin M. Reynolds Gerry S. Rivera Baisen Zeng Zahra Karimpourkalou Manith Norng Yulei Zhang Robayet Chowdhury Darlene Pedersen Melissa Pantoja Ellen Collarini Swetha Garimalla Shelley Izquierdo Eric G. Vajda Brett Antonio Devendra B. Srivastava Marie-Cecile van de Lavoir Yasmina Abdiche William Harriman Philip A. Leighton Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery mAbs Heavy chain-only sdab single-domain antibody transgenic chicken VHH |
| title | Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery |
| title_full | Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery |
| title_fullStr | Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery |
| title_full_unstemmed | Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery |
| title_short | Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery |
| title_sort | heavy chain only antibodies with a stabilized human vh in transgenic chickens for therapeutic antibody discovery |
| topic | Heavy chain-only sdab single-domain antibody transgenic chicken VHH |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2435476 |
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