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Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies.
Chew, Hui Yi; De Lima, Priscila O; Gonzalez Cruz, Jazmina L; Banushi, Blerida; Echejoh, Godwins; Hu, Lingbo; Joseph, Shannon R; Lum, Benedict; Rae, James; O'Donnell, Jake S; Merida de Long, Lilia; Okano, Satomi; King, Brigid; Barry, Rachael; Moi, Davide; Mazzieri, Roberta; Thomas, Ranjeny; Souza-Fonseca-Guimaraes, Fernando; Foote, Matthew; McCluskey, Adam; Robinson, Phillip J; Frazer, Ian H; Saunders, Nicholas A; Parton, Robert G; Dolcetti, Riccardo; Cuff, Katharine; Martin, Jennifer H; Panizza, Benedict; Walpole, Euan; Wells, James W; Simpson, Fiona.
Afiliação
  • Chew HY; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • De Lima PO; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Gonzalez Cruz JL; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Banushi B; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Echejoh G; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Hu L; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Joseph SR; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Lum B; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Rae J; Cell Biology and Molecular Medicine Division, Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia; Australia Centre for Microscopy and Microanalysis, University of Queensland, St Lucia QLD 4072, Australia.
  • O'Donnell JS; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Merida de Long L; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Okano S; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • King B; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Barry R; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Moi D; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Mazzieri R; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Thomas R; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Souza-Fonseca-Guimaraes F; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Foote M; Princess Alexandra Hospital, Brisbane QLD 4102, Australia.
  • McCluskey A; Centre for Chemistry, Biology and Clinical Pharmacology, The University of Newcastle, Callaghan NSW 2308, Australia.
  • Robinson PJ; Cell Signaling Unit, Children's Medical Research Institute, The University of Sydney, Sydney NSW 2145, Australia.
  • Frazer IH; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Saunders NA; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Parton RG; Cell Biology and Molecular Medicine Division, Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia; Australia Centre for Microscopy and Microanalysis, University of Queensland, St Lucia QLD 4072, Australia.
  • Dolcetti R; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Cuff K; Princess Alexandra Hospital, Brisbane QLD 4102, Australia; Faculty of Medicine, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Martin JH; Princess Alexandra Hospital, Brisbane QLD 4102, Australia; Centre for Chemistry, Biology and Clinical Pharmacology, The University of Newcastle, Callaghan NSW 2308, Australia.
  • Panizza B; Princess Alexandra Hospital, Brisbane QLD 4102, Australia; Faculty of Medicine, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Walpole E; Princess Alexandra Hospital, Brisbane QLD 4102, Australia; Faculty of Medicine, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Wells JW; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia.
  • Simpson F; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba QLD 4102, Australia. Electronic address: f.simpson@uq.edu.au.
Cell ; 180(5): 895-914.e27, 2020 03 05.
Article em En | MEDLINE | ID: mdl-32142680
ABSTRACT
A safe and controlled manipulation of endocytosis in vivo may have disruptive therapeutic potential. Here, we demonstrate that the anti-emetic/anti-psychotic prochlorperazine can be repurposed to reversibly inhibit the in vivo endocytosis of membrane proteins targeted by therapeutic monoclonal antibodies, as directly demonstrated by our human tumor ex vivo assay. Temporary endocytosis inhibition results in enhanced target availability and improved efficiency of natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC), a mediator of clinical responses induced by IgG1 antibodies, demonstrated here for cetuximab, trastuzumab, and avelumab. Extensive analysis of downstream signaling pathways ruled out on-target toxicities. By overcoming the heterogeneity of drug target availability that frequently characterizes poorly responsive or resistant tumors, clinical application of reversible endocytosis inhibition may considerably improve the clinical benefit of ADCC-mediating therapeutic antibodies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proclorperazina / Resistencia a Medicamentos Antineoplásicos / Citotoxicidade Celular Dependente de Anticorpos / Neoplasias Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proclorperazina / Resistencia a Medicamentos Antineoplásicos / Citotoxicidade Celular Dependente de Anticorpos / Neoplasias Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article