Exploration and Modulation of Antibody Fragment Biophysical Properties by Replacing the Framework Region Sequences
| Autor: | Thomas Cnudde, Marie-Noëlle Mévélec, Nicolas Aubrey, Corinne Henriquet, Martine Pugnière, Zineb Lakhrif, Matthieu O. Juste, Isabella Gizzi Jiacomini, Anne di Tommaso, Fanny Boursin, Isabelle Dimier-Poisson, Justine Bourgoin, Catherine Horiot |
|---|---|
| Přispěvatelé: | Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Laboratorio de Imunoquimica, Departamento de Patologia Basica, Universidade Federal do Paraná (UFPR), ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010), Chanteloup, Nathalie Katy, Laboratoires d'excellence - Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used - - MAbImprove2010 - ANR-10-LABX-0053 - LABX - VALID, Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine [SDV.IMM] Life Sciences [q-bio]/Immunology engineering [SDV]Life Sciences [q-bio] Immunology stabilities Article 03 medical and health sciences 0302 clinical medicine Fragment (logic) Drug Discovery Immunology and Allergy Molecule Framework region single-chain Fragment variable (scFv) chemistry.chemical_classification Protein L (PpL) biology Chemistry Prokaryote biology.organism_classification 3. Good health Amino acid [SDV] Life Sciences [q-bio] framework regions 030104 developmental biology 030220 oncology & carcinogenesis Yield (chemistry) biology.protein Biophysics [SDV.IMM]Life Sciences [q-bio]/Immunology production Antibody lcsh:RC581-607 Relevant information |
| Zdroj: | Antibodies Antibodies, MDPI, 2020, 9 (2), 17 p. ⟨10.3390/antib9020009⟩ Antibodies, Vol 9, Iss 9, p 9 (2020) Volume 9 Issue 2 |
| ISSN: | 2073-4468 |
| DOI: | 10.3390/antib9020009⟩ |
| Popis: | In order to increase the successful development of recombinant antibodies and fragments, it seems fundamental to enhance their expression and/or biophysical properties, such as the thermal, chemical, and pH stabilities. In this study, we employed a method bases on replacing the antibody framework region sequences, in order to promote more particularly single-chain Fragment variable (scFv) product quality. We provide evidence that mutations of the VH- C-C&prime loop might significantly improve the prokaryote production of well-folded and functional fragments with a production yield multiplied by 27 times. Additional mutations are accountable for an increase in the thermal (+19.6 ° C) and chemical (+1.9 M) stabilities have also been identified. Furthermore, the hereby-produced fragments have shown to remain stable at a pH of 2.0, which avoids molecule functional and structural impairments during the purification process. Lastly, this study provides relevant information to the understanding of the relationship between the antibodies amino acid sequences and their respective biophysical properties. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|