Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | mAbs, Vol 16, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 19420862 1942-0870 1942-0862 |
| DOI: | 10.1080/19420862.2024.2435476 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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