Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies

• Published in: Cell Vol. 180; no. 5; pp. 895 - 914.e27
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2020
• Subjects: antibody-dependent cellular cytotoxicity; avelumab; cetuximab; endocytosis; epidermal growth factor receptor; monoclonal antibody therapy; natural killer cell; prochlorperazine; programmed death ligand 1; trastuzumab; trastuzumab; prochlorperazine; antibody-dependent cellular cytotoxicity; avelumab; epidermal growth factor receptor; endocytosis; cetuximab; programmed death ligand 1; monoclonal antibody therapy; natural killer cell

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 antib...