Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer.
Fiche publication
Date publication
décembre 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DETAPPE Alexandre
Tous les auteurs :
Qi R, Wang Y, Bruno PM, Xiao H, Yu Y, Li T, Lauffer S, Wei W, Chen Q, Kang X, Song H, Yang X, Huang X, Detappe A, Matulonis U, Pepin D, Hemann MT, Birrer MJ, Ghoroghchian PP
Lien Pubmed
Résumé
Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly increase loading on a per-vehicle basis as compared to antibody-drug conjugates (ADCs). Their intraperitoneal administration enabled triggered release of the active MMAE toxin to inhibit tumor growth and to extend animal survival to >90 days in a cell-line xenograft model of disseminated ovarian cancer. In a patient-derived xenograft model of advanced-stage and platinum-resistant ovarian cancer, an MMAE-based NDC doubled the duration of tumor growth inhibition as compared to cisplatin. NDCs of highly potent toxins thus introduce a translatable platform that may be exploited to maximize the safety and efficacy of cytotoxic chemotherapies, combining the best features of ADCs with those of nanoparticle-based therapeutics.
Mots clés
Animals, Antineoplastic Agents, pharmacology, Cell Line, Tumor, Cisplatin, pharmacology, Drug Resistance, Neoplasm, drug effects, Female, Humans, Immunoconjugates, chemistry, Mice, Inbred BALB C, Mice, Nude, Nanoparticles, chemistry, Ovarian Neoplasms, drug therapy, Survival Analysis, Treatment Outcome, Xenograft Model Antitumor Assays
Référence
Nat Commun. 2017 12 18;8(1):2166