RUBY® - a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties
Despite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a novel bispecific antibody format that allows rapid generation of bsAbs that fulfill key development criteria. The RUBYTM format has a 2 + 2 geometry, where two Fab fragments are linked via their light chains to the C-termini of an IgG, and carries mutations for optimal chain pairing. The unique design enables generation of bsAbs with mAb-like attributes. Our data demonstrate that RUBY bsAbs are compatible with small-scale production systems for screening purposes and can be produced at high yields (>3 g/L) from stable cell lines. The bsAbs produced are shown to, in general, contain low amounts of aggregates and display favorable solubility and stress endurance profiles. Further, compatibility with various IgG isotypes is shown and tailored Fc gamma receptor binding confirmed. Also, retained interaction with FcRn is demonstrated to translate into a pharmacokinetic profile in mice and non-human primates that is comparable to mAb controls. Functionality of conditional active RUBY bsAbs is confirmed in vitro. Anti-tumor effects in vivo have previously been demonstrated, and shown to be superior to a comparable mAb, and here it is further shown that RUBY bsAbs penetrate and localize to tumor tissue in vivo. In all, the RUBY format has attractive mAb-like attributes and offers the possibility to mitigate many of the development challenges linked to other bsAb formats, facilitating both high functionality and developability.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
mAbs - 16(2024), 1 vom: 25. Jan., Seite 2330113 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nyesiga, Barnabas [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies, Bispecific |
|---|
| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/19420862.2024.2330113 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370175298 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370175298 | ||
| 003 | DE-627 | ||
| 005 | 20240329000948.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240327s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/19420862.2024.2330113 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1353.xml |
| 035 | |a (DE-627)NLM370175298 | ||
| 035 | |a (NLM)38527972 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nyesiga, Barnabas |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a RUBY® - a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.03.2024 | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Despite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a novel bispecific antibody format that allows rapid generation of bsAbs that fulfill key development criteria. The RUBYTM format has a 2 + 2 geometry, where two Fab fragments are linked via their light chains to the C-termini of an IgG, and carries mutations for optimal chain pairing. The unique design enables generation of bsAbs with mAb-like attributes. Our data demonstrate that RUBY bsAbs are compatible with small-scale production systems for screening purposes and can be produced at high yields (>3 g/L) from stable cell lines. The bsAbs produced are shown to, in general, contain low amounts of aggregates and display favorable solubility and stress endurance profiles. Further, compatibility with various IgG isotypes is shown and tailored Fc gamma receptor binding confirmed. Also, retained interaction with FcRn is demonstrated to translate into a pharmacokinetic profile in mice and non-human primates that is comparable to mAb controls. Functionality of conditional active RUBY bsAbs is confirmed in vitro. Anti-tumor effects in vivo have previously been demonstrated, and shown to be superior to a comparable mAb, and here it is further shown that RUBY bsAbs penetrate and localize to tumor tissue in vivo. In all, the RUBY format has attractive mAb-like attributes and offers the possibility to mitigate many of the development challenges linked to other bsAb formats, facilitating both high functionality and developability | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antibody format | |
| 650 | 4 | |a IgG | |
| 650 | 4 | |a RUBY® | |
| 650 | 4 | |a bispecific antibodies | |
| 650 | 4 | |a immuno-oncology | |
| 650 | 4 | |a tetravalent | |
| 650 | 7 | |a Antibodies, Bispecific |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 700 | 1 | |a Levin, Mattias |e verfasserin |4 aut | |
| 700 | 1 | |a Säll, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Rosén, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Jansson, Kim |e verfasserin |4 aut | |
| 700 | 1 | |a Fritzell, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Hägerbrand, Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Weilguny, Dietmar |e verfasserin |4 aut | |
| 700 | 1 | |a von Schantz, Laura |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t mAbs |d 2009 |g 16(2024), 1 vom: 25. Jan., Seite 2330113 |w (DE-627)NLM194097110 |x 1942-0870 |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2024 |g number:1 |g day:25 |g month:01 |g pages:2330113 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/19420862.2024.2330113 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2024 |e 1 |b 25 |c 01 |h 2330113 | ||