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Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition.
Priem, Bram; van Leent, Mandy M T; Teunissen, Abraham J P; Sofias, Alexandros Marios; Mourits, Vera P; Willemsen, Lisa; Klein, Emma D; Oosterwijk, Roderick S; Meerwaldt, Anu E; Munitz, Jazz; Prévot, Geoffrey; Vera Verschuur, Anna; Nauta, Sheqouia A; van Leeuwen, Esther M; Fisher, Elizabeth L; de Jong, Karen A M; Zhao, Yiming; Toner, Yohana C; Soultanidis, Georgios; Calcagno, Claudia; Bomans, Paul H H; Friedrich, Heiner; Sommerdijk, Nico; Reiner, Thomas; Duivenvoorden, Raphaël; Zupancic, Eva; Di Martino, Julie S; Kluza, Ewelina; Rashidian, Mohammad; Ploegh, Hidde L; Dijkhuizen, Rick M; Hak, Sjoerd; Pérez-Medina, Carlos; Bravo-Cordero, Jose Javier; de Winther, Menno P J; Joosten, Leo A B; van Elsas, Andrea; Fayad, Zahi A; Rialdi, Alexander; Torre, Denis; Guccione, Ernesto; Ochando, Jordi; Netea, Mihai G; Griffioen, Arjan W; Mulder, Willem J M.
Afiliação
  • Priem B; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medical Biochemistry, Experimental Vascular Biology, A
  • van Leent MMT; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medical Biochemistry, Experimental Vascular Biology, A
  • Teunissen AJP; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Sofias AM; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Circulation and Medical Imaging, Faculty of Medicine a
  • Mourits VP; Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Willemsen L; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands.
  • Klein ED; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Oosterwijk RS; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Meerwaldt AE; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Biomedical MR Imaging and Spectroscopy Group, Center for Image Scien
  • Munitz J; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Prévot G; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Vera Verschuur A; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Nauta SA; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • van Leeuwen EM; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Fisher EL; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • de Jong KAM; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Zhao Y; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Toner YC; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Soultanidis G; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Calcagno C; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bomans PHH; Department of Chemical Engineering and Chemistry, Center for Multiscale Electron Microscopy and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
  • Friedrich H; Department of Chemical Engineering and Chemistry, Center for Multiscale Electron Microscopy and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
  • Sommerdijk N; Department of Biochemistry, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Reiner T; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
  • Duivenvoorden R; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Nephrology, Radboud Institute for Molecular Life Scien
  • Zupancic E; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Di Martino JS; Department of Medicine, Division of Hematology and Medical Oncology, Icahn School of Medicine, Tisch Cancer Institute at Mount Sinai, New York, NY, USA.
  • Kluza E; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands.
  • Rashidian M; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Ploegh HL; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Dijkhuizen RM; Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, the Netherlands.
  • Hak S; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Pérez-Medina C; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madr
  • Bravo-Cordero JJ; Department of Medicine, Division of Hematology and Medical Oncology, Icahn School of Medicine, Tisch Cancer Institute at Mount Sinai, New York, NY, USA.
  • de Winther MPJ; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands; Institute for Cardiovascular Prevention (IPEK), Munich, Germany.
  • Joosten LAB; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • van Elsas A; Aduro Biotech, Inc., Berkeley, CA, USA.
  • Fayad ZA; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rialdi A; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Torre D; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Guccione E; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pharmacological Sciences and Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Ochando J; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Transplant Immunology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Netea MG; Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Craiova, Romania; Department for Immunology & Metabolism, Life and Medical Sciences Ins
  • Griffioen AW; Department of Medical Oncology (NA Angiogenesis Laboratory), Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands.
  • Mulder WJM; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Moun
Cell ; 183(3): 786-801.e19, 2020 10 29.
Article em En | MEDLINE | ID: mdl-33125893
ABSTRACT
Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP10-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP10-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP10-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Melanoma Experimental / Nanotecnologia / Inibidores de Checkpoint Imunológico / Imunidade Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Melanoma Experimental / Nanotecnologia / Inibidores de Checkpoint Imunológico / Imunidade Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article