Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies
| Autor: | Starlynn C, Clarke, Biao, Ma, Nathan D, Trinklein, Ute, Schellenberger, Michael J, Osborn, Laure-Hélène, Ouisse, Andrew, Boudreau, Laura M, Davison, Katherine E, Harris, Harshad S, Ugamraj, Aarti, Balasubramani, Kevin H, Dang, Brett, Jorgensen, Heather Anne N, Ogana, Duy T, Pham, Payal P, Pratap, Preethi, Sankaran, Ignacio, Anegon, Wim C, van Schooten, Marianne, Brüggemann, Roland, Buelow, Shelley, Force Aldred |
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| Přispěvatelé: | Le Bihan, Sylvie, Teneobio, Inc. [Menlo Park, CA, USA], Genetic and Cellular Engineering in Immunology and Regenerative Medicine (Team 2 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
Immunology Antibody Affinity Immunoglobulin Variable Region CHO Cells Protein Engineering Antibodies Protein Structure Secondary Cricetulus B cell development Animals Humans Immunology and Allergy transgenic rats VH domains Antigens repertoire sequencing antibody discovery platform Original Research B-Lymphocytes Crystallography [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology heavy chain antibodies High-Throughput Nucleotide Sequencing Single-Domain Antibodies Flow Cytometry Rats Genetic Loci domain antibodies Immunization Immunoglobulin Light Chains next-generation sequencing Rats Transgenic Immunoglobulin Heavy Chains lcsh:RC581-607 [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Frontiers in Immunology, Vol 9 (2019) Frontiers in Immunology Frontiers in Immunology, 2019, 9, pp.3037. ⟨10.3389/fimmu.2018.03037⟩ |
| ISSN: | 1664-3224 |
| Popis: | International audience; Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V H regions are functional as single domains, forming the smallest active antibody fragment. These V[H] regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human V[H] regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human V[H] domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules. |
| Databáze: | OpenAIRE |
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