Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells
Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells
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 three high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis (ADCP). For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography (PET) in novel hSIRPα/hCD47 knock-in (KI) 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 probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.
Rothbauer Ulrich、Blaess Simone、Maurer Andreas、Wagner Teresa R.、Rezza Am¨|lie、Thiam Kader、Pezzana Stefania、Scholz Armin M.、Nueske Stefan、Sonanini Dominik、Kneilling Manfred、Zeck Anne、Pichler Bernd J.、Traenkle Bjoern、Seyfried Dominik、Frecot Desiree I.、Leske Inga B.、Maier Sandra、Kaiser Philipp D.、Gramlich Marius、S?nego Fabiane、Gouttefangeas C¨|cile
NMI Natural and Medical Sciences Institute at the University of T¨1bingen||Eberhard Karls University T¨1bingen||University of T¨1bingenWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingenWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingen||University of T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingengenOwaygenOwayWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingenLivestock Center of the Faculty of Veterinary Medicine, Ludwig Maximilians University MunichLivestock Center of the Faculty of Veterinary Medicine, Ludwig Maximilians University MunichWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingen||Department of Medical Oncology and Pneumology, University of T¨1bingenWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingen||University of T¨1bingen||Department of Dermatology, University of T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingenWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingen||University of T¨1bingen||German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingenWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingen||Eberhard Karls University T¨1bingenEberhard Karls University T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingenNMI Natural and Medical Sciences Institute at the University of T¨1bingengenOwayDepartment of Immunology, Institute of Cell Biology, University of T¨1bingen||University of T¨1bingen||German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site T¨1bingen
医药卫生理论医学研究方法肿瘤学
Rothbauer Ulrich,Blaess Simone,Maurer Andreas,Wagner Teresa R.,Rezza Am¨|lie,Thiam Kader,Pezzana Stefania,Scholz Armin M.,Nueske Stefan,Sonanini Dominik,Kneilling Manfred,Zeck Anne,Pichler Bernd J.,Traenkle Bjoern,Seyfried Dominik,Frecot Desiree I.,Leske Inga B.,Maier Sandra,Kaiser Philipp D.,Gramlich Marius,S?nego Fabiane,Gouttefangeas C¨|cile.Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells[EB/OL].(2025-03-28)[2025-06-04].https://www.biorxiv.org/content/10.1101/2023.06.27.546763.点此复制
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