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Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer.
Qi, Ruogu; Wang, Yongheng; Bruno, Peter M; Xiao, Haihua; Yu, Yingjie; Li, Ting; Lauffer, Sam; Wei, Wei; Chen, Qixian; Kang, Xiang; Song, Haiqin; Yang, Xi; Huang, Xing; Detappe, Alexandre; Matulonis, Ursula; Pepin, David; Hemann, Michael T; Birrer, Michael J; Ghoroghchian, P Peter.
Afiliação
  • Qi R; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Wang Y; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Bruno PM; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Xiao H; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Yu Y; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Li T; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Lauffer S; Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
  • Wei W; Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
  • Chen Q; Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
  • Kang X; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Song H; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Yang X; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Huang X; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Detappe A; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Matulonis U; Koch Institute for Integrative Cancer Research at MIT, 500 Main Street, Cambridge, MA, 02139, USA.
  • Pepin D; Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
  • Hemann MT; Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
  • Birrer MJ; Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
  • Ghoroghchian PP; Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
Nat Commun ; 8(1): 2166, 2017 12 18.
Article em En | MEDLINE | ID: mdl-29255160
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cisplatino / Imunoconjugados / Resistencia a Medicamentos Antineoplásicos / Ensaios Antitumorais Modelo de Xenoenxerto / Nanopartículas Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cisplatino / Imunoconjugados / Resistencia a Medicamentos Antineoplásicos / Ensaios Antitumorais Modelo de Xenoenxerto / Nanopartículas Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article