Frontiers in Immunology (Jun 2023)
A novel ACE2 decoy for both neutralization of SARS-CoV-2 variants and killing of infected cells
- Alexandra Kegler,
- Laura Drewitz,
- Claudia Arndt,
- Claudia Arndt,
- Cansu Daglar,
- Liliana Rodrigues Loureiro,
- Nicola Mitwasi,
- Christin Neuber,
- Karla Elizabeth González Soto,
- Tabea Bartsch,
- Larysa Baraban,
- Holger Ziehr,
- Markus Heine,
- Annabel Nieter,
- Andres Moreira-Soto,
- Arne Kühne,
- Jan Felix Drexler,
- Barbara Seliger,
- Barbara Seliger,
- Markus Laube,
- Domokos Máthé,
- Domokos Máthé,
- Domokos Máthé,
- Bernadett Pályi,
- Polett Hajdrik,
- László Forgách,
- Zoltán Kis,
- Krisztián Szigeti,
- Ralf Bergmann,
- Ralf Bergmann,
- Anja Feldmann,
- Anja Feldmann,
- Anja Feldmann,
- Michael Bachmann,
- Michael Bachmann,
- Michael Bachmann
Affiliations
- Alexandra Kegler
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Laura Drewitz
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Claudia Arndt
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Claudia Arndt
- Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Cansu Daglar
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Liliana Rodrigues Loureiro
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Nicola Mitwasi
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Christin Neuber
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Karla Elizabeth González Soto
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Tabea Bartsch
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Larysa Baraban
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Holger Ziehr
- Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Braunschweig, Germany
- Markus Heine
- Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Braunschweig, Germany
- Annabel Nieter
- Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Braunschweig, Germany
- Andres Moreira-Soto
- Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Arne Kühne
- Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Jan Felix Drexler
- Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Barbara Seliger
- Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle, Germany
- Barbara Seliger
- Institute of Translational Immunology, Medical High School, Brandenburg an der Havel, Germany
- Markus Laube
- Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Domokos Máthé
- Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Domokos Máthé
- Hungarian Centre of Excellence for Molecular Medicine, In Vivo Imaging Advanced Core Facility, Szeged, Hungary
- Domokos Máthé
- 0CROmed Translational Research Ltd., Budapest, Hungary
- Bernadett Pályi
- 1National Biosafety Laboratory, Division of Microbiological Reference Laboratories, National Public Health Center, Budapest, Hungary
- Polett Hajdrik
- Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- László Forgách
- 2Semmelweis University School of Pharmacy, Semmelweis University, Budapest, Hungary
- Zoltán Kis
- 1National Biosafety Laboratory, Division of Microbiological Reference Laboratories, National Public Health Center, Budapest, Hungary
- Krisztián Szigeti
- Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Ralf Bergmann
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Ralf Bergmann
- Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Anja Feldmann
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Anja Feldmann
- 3National Center for Tumor Diseases Dresden (NCT), German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Anja Feldmann
- 4German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Michael Bachmann
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Michael Bachmann
- 3National Center for Tumor Diseases Dresden (NCT), German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Michael Bachmann
- 4German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1204543
- Journal volume & issue
-
Vol. 14
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to millions of infections and deaths worldwide. As this virus evolves rapidly, there is a high need for treatment options that can win the race against new emerging variants of concern. Here, we describe a novel immunotherapeutic drug based on the SARS-CoV-2 entry receptor ACE2 and provide experimental evidence that it cannot only be used for (i) neutralization of SARS-CoV-2 in vitro and in SARS-CoV-2-infected animal models but also for (ii) clearance of virus-infected cells. For the latter purpose, we equipped the ACE2 decoy with an epitope tag. Thereby, we converted it to an adapter molecule, which we successfully applied in the modular platforms UniMAB and UniCAR for retargeting of either unmodified or universal chimeric antigen receptor-modified immune effector cells. Our results pave the way for a clinical application of this novel ACE2 decoy, which will clearly improve COVID-19 treatment.
Keywords
