Fibronectin extra domain A as a drug delivery targeting epitope for rheumatoid arthritis.


Journal

Advances in rheumatology (London, England)
ISSN: 2523-3106
Titre abrégé: Adv Rheumatol
Pays: England
ID NLM: 101734172

Informations de publication

Date de publication:
27 05 2022
Historique:
received: 28 05 2021
accepted: 15 05 2022
entrez: 27 5 2022
pubmed: 28 5 2022
medline: 1 6 2022
Statut: epublish

Résumé

To assess the ability of monoclonal antibodies (mAbs) specific for fibronectin extra-domain A (FnEDA) to target diseased tissues of mouse collagen induced arthritis (mCIA) models. To explore the parameters of the targeting exhibited by anti-FnEDA mAbs including timing and location. Targeting capabilities of anti-FnEDA mAbs were demonstrated by biodistribution study where i.v. injected antibodies were detected by conjugated near-infrared (NIR) fluorophore, Anti-FnEDA mAbs show specific targeting to diseased paws of mCIA animal. The targeting was focused on inflamed synovium which is consistent with FnEDA expression profile in both mCIA and human RA tissues. Anti-FnEDA mAbs accumulated in diseased tissue at pharmacologically relevant concentrations, the targeting was sustained for up to 14 days and FnEDA was able to support targeting of multiple doses of anti-FnEDA mAbs given 5 days apart. FnEDA is specifically upregulated in the inflamed tissues of mCIA. Antibodies specific for FnEDA can be useful as molecular delivery vehicles for disease specific targeting of payloads to inflamed joint tissue.

Identifiants

pubmed: 35624488
doi: 10.1186/s42358-022-00247-2
pii: 10.1186/s42358-022-00247-2
doi:

Substances chimiques

Antibodies, Monoclonal 0
Epitopes 0
Fibronectins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17

Informations de copyright

© 2022. The Author(s).

Références

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Auteurs

Victor Z Sun (VZ)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA. victor.sun@abbvie.com.

Terry L Melim (TL)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Soumya Mitra (S)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Jamie E Erickson (JE)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Shaughn H Bryant (SH)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Avery Farnham (A)

Generate Biomedicines, Cambridge, MA, USA.

Susan Westmoreland (S)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Heather Knight (H)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Liang Zhang (L)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Wendy Ritacco (W)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Kristoff Homan (K)

Bristol Myers Squibb, Boston, MA, USA.

Lorenzo Benatuil (L)

Dragonfly Therapeutics Inc, Waltham, MA, USA.

Annette J Schwartz Sterman (AJS)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

Andrew D Goodearl (AD)

Drug Discovery Science and Technology, Abbvie Bioresearch Center, Worcester, MA, USA.

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