A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability
We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determinin...
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| Format: | Article |
| 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/10.1080/19420862.2024.2394230 |
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| author | Fortunato Ferrara Adeline Fanni Andre A. R. Teixeira Esteban Molina Camila Leal-Lopes Ashley DeAguero Sara D’Angelo M. Frank Erasmus Laura Spector Luis Antonio Rodriguez Carnero Jianquan Li Thomas J. Pohl Nikolai Suslov Klervi Desrumeaux Conor McMahon Sagar Kathuria Andrew R. M. Bradbury |
| author_facet | Fortunato Ferrara Adeline Fanni Andre A. R. Teixeira Esteban Molina Camila Leal-Lopes Ashley DeAguero Sara D’Angelo M. Frank Erasmus Laura Spector Luis Antonio Rodriguez Carnero Jianquan Li Thomas J. Pohl Nikolai Suslov Klervi Desrumeaux Conor McMahon Sagar Kathuria Andrew R. M. Bradbury |
| author_sort | Fortunato Ferrara |
| collection | DOAJ |
| description | We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determining regions purged of sequence liabilities were inserted, and the use of phage and yeast display to carry out antibody selection. In addition to being developable, antibodies generated using our platform were extremely diverse, with most campaigns yielding sub-nanomolar binders. Here, we describe a platform advancement that incorporates Fab phage display followed by single-chain antibody-binding fragment Fab (scFab) yeast display. The scFab single-gene format provides balanced expression of light and heavy chains, with enhanced conversion to IgG, thereby combining the advantages of scFvs and Fabs. A meticulously engineered, quality-controlled Fab phage library was created using design principles similar to those used to create the scFv library. A diverse panel of binding scFabs, with high conversion efficiency to IgG, was isolated against two targets. This study highlights the compatibility of phage and yeast display with a Fab semi-synthetic library design, offering an efficient approach to generate drug-like antibodies directly, facilitating their conversion to potential therapeutic candidates. |
| format | Article |
| id | doaj-art-08adf8bbba7940a8b4cc3c5378c32316 |
| 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-08adf8bbba7940a8b4cc3c5378c323162025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2394230A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developabilityFortunato Ferrara0Adeline Fanni1Andre A. R. Teixeira2Esteban Molina3Camila Leal-Lopes4Ashley DeAguero5Sara D’Angelo6M. Frank Erasmus7Laura Spector8Luis Antonio Rodriguez Carnero9Jianquan Li10Thomas J. Pohl11Nikolai Suslov12Klervi Desrumeaux13Conor McMahon14Sagar Kathuria15Andrew R. M. Bradbury16Specifica LLC, a Q2 Solutions Company, Santa Fe, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USANew Mexico Consortium, Los Alamos, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USANew Mexico Consortium, Los Alamos, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USANew Mexico Consortium, Los Alamos, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USASanofi, Large Molecule Research, Cambridge, MA, USASanofi, Large Molecule Research, Vitry-sur-Seine, FranceSanofi, Large Molecule Research, Cambridge, MA, USASanofi, Large Molecule Research, Cambridge, MA, USASpecifica LLC, a Q2 Solutions Company, Santa Fe, NM, USAWe previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determining regions purged of sequence liabilities were inserted, and the use of phage and yeast display to carry out antibody selection. In addition to being developable, antibodies generated using our platform were extremely diverse, with most campaigns yielding sub-nanomolar binders. Here, we describe a platform advancement that incorporates Fab phage display followed by single-chain antibody-binding fragment Fab (scFab) yeast display. The scFab single-gene format provides balanced expression of light and heavy chains, with enhanced conversion to IgG, thereby combining the advantages of scFvs and Fabs. A meticulously engineered, quality-controlled Fab phage library was created using design principles similar to those used to create the scFv library. A diverse panel of binding scFabs, with high conversion efficiency to IgG, was isolated against two targets. This study highlights the compatibility of phage and yeast display with a Fab semi-synthetic library design, offering an efficient approach to generate drug-like antibodies directly, facilitating their conversion to potential therapeutic candidates.https://www.tandfonline.com/doi/10.1080/19420862.2024.2394230Recombinant antibody librariesFabphage displayyeast displaydevelopability |
| spellingShingle | Fortunato Ferrara Adeline Fanni Andre A. R. Teixeira Esteban Molina Camila Leal-Lopes Ashley DeAguero Sara D’Angelo M. Frank Erasmus Laura Spector Luis Antonio Rodriguez Carnero Jianquan Li Thomas J. Pohl Nikolai Suslov Klervi Desrumeaux Conor McMahon Sagar Kathuria Andrew R. M. Bradbury A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability mAbs Recombinant antibody libraries Fab phage display yeast display developability |
| title | A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability |
| title_full | A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability |
| title_fullStr | A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability |
| title_full_unstemmed | A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability |
| title_short | A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability |
| title_sort | next generation fab library platform directly yielding drug like antibodies with high affinity diversity and developability |
| topic | Recombinant antibody libraries Fab phage display yeast display developability |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2394230 |
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