A novel IgG Fc by computer-aided design enhances heavy-chain heterodimerization in bi- or trispecific antibodies
© The Author(s) 2022. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissionsoup.com..
The classical `knob-into-holes' (KIH) strategy (knob(T366Y)/hole (Y407T)) has successfully enhanced the heterodimerization of a bispecific antibody (BsAb) resulting in heterodimer formation up to 92% of protein A (ProA)-purified protein pool. However, it does not show high efficiency for every BsAb. KIH was initially applied to a CD20/CD3 BsAb. After in silico modeling, two additional new mutations, S354Y in knob-heavy chain (HC) and Q347E in hole-HC, together with KIH named `ETYY', were introduced in the Fc. The CD20/CD3 BsAb hybrid only represented ~ 50% of the ProA-purified protein pool when KIH was applied. With ETYY, the percentage of CD20/CD3 hybrid increased to 93.8%. CD20/CD3-v4b (containing ETYY) retains the original activity of the BsAb at both Fab and Fc regions, and also shows good developability. These results indicate that the computer-aided novel ETYY design has the potential to improve the development of next-generation BsAbs with higher yields and simpler purification.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Antibody therapeutics - 5(2022), 3 vom: 01. Juli, Seite 216-225 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Bo [VerfasserIn] |
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| Links: |
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| Themen: |
Bispecific antibodies |
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| Anmerkungen: |
Date Revised 06.09.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1093/abt/tbac019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345600614 |
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| 245 | 1 | 2 | |a A novel IgG Fc by computer-aided design enhances heavy-chain heterodimerization in bi- or trispecific antibodies |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a The classical `knob-into-holes' (KIH) strategy (knob(T366Y)/hole (Y407T)) has successfully enhanced the heterodimerization of a bispecific antibody (BsAb) resulting in heterodimer formation up to 92% of protein A (ProA)-purified protein pool. However, it does not show high efficiency for every BsAb. KIH was initially applied to a CD20/CD3 BsAb. After in silico modeling, two additional new mutations, S354Y in knob-heavy chain (HC) and Q347E in hole-HC, together with KIH named `ETYY', were introduced in the Fc. The CD20/CD3 BsAb hybrid only represented ~ 50% of the ProA-purified protein pool when KIH was applied. With ETYY, the percentage of CD20/CD3 hybrid increased to 93.8%. CD20/CD3-v4b (containing ETYY) retains the original activity of the BsAb at both Fab and Fc regions, and also shows good developability. These results indicate that the computer-aided novel ETYY design has the potential to improve the development of next-generation BsAbs with higher yields and simpler purification | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Fc engineering | |
| 650 | 4 | |a bispecific antibodies | |
| 650 | 4 | |a computer-aided antibody design | |
| 650 | 4 | |a heavy chain heterodimerization | |
| 650 | 4 | |a knob-into-hole | |
| 650 | 4 | |a multi-specific antibodies | |
| 650 | 4 | |a trispecific antibodies | |
| 700 | 1 | |a Lin, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Hoag, Matthew R |e verfasserin |4 aut | |
| 700 | 1 | |a Wright, Meredith |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Mingjun |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Wenyan |e verfasserin |4 aut | |
| 700 | 1 | |a Gallolu Kankanamalage, Sachith |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yue |e verfasserin |4 aut | |
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