Fiche publication
Date publication
octobre 2025
Journal
Biomacromolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah
,
Dr WAGNER Alain
,
Dr KOLODYCH Sergii
,
Dr KONIEV Sasha
,
Dr CHAUBET Guilhem
Tous les auteurs :
Lehot V, Lidický O, Most J, Nothisen M, Erb S, Dovgan I, Osypenko A, Koniev O, Kolodych S, Kotrchová L, Chaubet G, Cianférani S, Etrych T, Wagner A
Lien Pubmed
Résumé
In the past two decades, antibody-drug conjugates (ADCs) have emerged as highly effective targeted therapeutics against cancers. One current path to improve ADCs is to increase the amount of cytotoxic payload delivered to cancer cells by conjugating antibodies with a soluble polymer bearing several drug molecules. However, this approach is challenging due to the high molecular weight of the polymer and the need to strictly control the degree of conjugation to maintain favorable pharmacokinetic and binding profiles. Here, we build from the recent development brought to our automated stoichiometric conjugation device to tackle this challenge. We produced a new format of ADC-like targeted therapy: monoconjugated Antibody-Polymer-Drug Conjugates (APDCs) with enzyme-cleavable linkers, designed to achieve selective delivery of the cytotoxic MMAE to HER2 cancer cells. We showed the selectivity of our conjugates for HER2 over HER2 cells in vitro and demonstrated their efficiency in vivo in a SKBR-3-xenografted mouse (NOD-SCID) model.
Référence
Biomacromolecules. 2025 10 13;:
