Development and evaluation of β-galactosidase-sensitive antibody-drug conjugates.
Fiche publication
Date publication
août 2017
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah, Dr MULLER Christian, Dr WAGNER Alain, Dr KOLODYCH Sergii, Dr KONIEV Sasha, Dr KREZEL Wojciech
Tous les auteurs :
Kolodych S, Michel C, Delacroix S, Koniev O, Ehkirch A, Eberova J, Cianférani S, Renoux B, Krezel W, Poinot P, Muller CD, Papot S, Wagner A
Lien Pubmed
Résumé
The selective destruction of tumour cells while sparing healthy tissues is one of the main challenges in cancer therapy. Antibody-drug conjugates (ADCs) are arguably the most rapidly expanding class of targeted cancer therapies. Efficient drug conjugation and release technologies are essential for the development of these new therapeutic agents. In response to the ever-increasing demand for efficient drug release systems, we have developed a new class of β-galactosidase-cleavable linkers for ADCs. Within this framework, novel payloads comprising a galactoside linker, the monomethyl auristatin E (MMAE) and cysteine-reactive groups were synthesized, conjugated with trastuzumab and evaluated both in vitro and in vivo. The ADCs with galactoside linkers demonstrated superior therapeutic efficacy in mice compared to the marketed trastuzumab emtansine used for the treatment of breast cancer.
Mots clés
Antibody-drug conjugate, Cancer, Chemotherapy, Drug delivery, Enzyme-responsive systems, Self-immolative linker
Référence
Eur J Med Chem. 2017 Aug;: