Frontiers in Immunology (Dec 2023)
Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells
- Teresa R. Wagner,
- Teresa R. Wagner,
- Simone Blaess,
- Inga B. Leske,
- Desiree I. Frecot,
- Desiree I. Frecot,
- Marius Gramlich,
- Bjoern Traenkle,
- Philipp D. Kaiser,
- Dominik Seyfried,
- Dominik Seyfried,
- Sandra Maier,
- Amélie Rezza,
- Fabiane Sônego,
- Kader Thiam,
- Stefania Pezzana,
- Anne Zeck,
- Cécile Gouttefangeas,
- Cécile Gouttefangeas,
- Cécile Gouttefangeas,
- Armin M. Scholz,
- Stefan Nueske,
- Andreas Maurer,
- Andreas Maurer,
- Manfred Kneilling,
- Manfred Kneilling,
- Manfred Kneilling,
- Bernd J. Pichler,
- Bernd J. Pichler,
- Bernd J. Pichler,
- Dominik Sonanini,
- Dominik Sonanini,
- Ulrich Rothbauer,
- Ulrich Rothbauer
Affiliations
- Teresa R. Wagner
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Teresa R. Wagner
- Pharmaceutical Biotechnology, Eberhard Karls University Tübingen, Tübingen, Germany
- Simone Blaess
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Inga B. Leske
- Pharmaceutical Biotechnology, Eberhard Karls University Tübingen, Tübingen, Germany
- Desiree I. Frecot
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Desiree I. Frecot
- Pharmaceutical Biotechnology, Eberhard Karls University Tübingen, Tübingen, Germany
- Marius Gramlich
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Bjoern Traenkle
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Philipp D. Kaiser
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Dominik Seyfried
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Dominik Seyfried
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany
- Sandra Maier
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Amélie Rezza
- Preclinical Models & Services, genOway, Lyon, France
- Fabiane Sônego
- Preclinical Models & Services, genOway, Lyon, France
- Kader Thiam
- Preclinical Models & Services, genOway, Lyon, France
- Stefania Pezzana
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Anne Zeck
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Cécile Gouttefangeas
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany
- Cécile Gouttefangeas
- Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen, Germany
- Cécile Gouttefangeas
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Armin M. Scholz
- Livestock Center of the Faculty of Veterinary Medicine, Ludwig Maximilians University Munich, Oberschleissheim, Germany
- Stefan Nueske
- Livestock Center of the Faculty of Veterinary Medicine, Ludwig Maximilians University Munich, Oberschleissheim, Germany
- Andreas Maurer
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Andreas Maurer
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Manfred Kneilling
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Manfred Kneilling
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Manfred Kneilling
- Department of Dermatology, University of Tübingen, Tübingen, Germany
- Bernd J. Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Bernd J. Pichler
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany
- Bernd J. Pichler
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Dominik Sonanini
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Dominik Sonanini
- 0Department of Medical Oncology and Pneumology, University of Tübingen, Tübingen, Germany
- Ulrich Rothbauer
- Pharmaceutical Biotechnology, Eberhard Karls University Tübingen, Tübingen, Germany
- Ulrich Rothbauer
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1264179
- Journal volume & issue
-
Vol. 14
Abstract
Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the “don’t eat me” ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)–specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis. For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography in novel hSIRPα/hCD47 knock-in mice, we demonstrated the applicability of 64Cu-hSIRPα-S36 Nb to visualize tumor infiltration of myeloid cells. We envision that the hSIRPα-Nbs presented in this study have potential as versatile theranostic probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.
Keywords
- nanobodies (Nbs)
- SIRPalpha
- myeloid cells
- PET imaging tracer
- immune checkpoint inhibitor (ICI)
- theranostics
