Author:
Wagner Teresa R.,Blaess Simone,Leske Inga B.,Frecot Desiree I.,Gramlich Marius,Traenkle Bjoern,Kaiser Philipp D.,Seyfried Dominik,Maier Sandra,Rezza Amélie,Sônego Fabiane,Thiam Kader,Pezzana Stefania,Zeck Anne,Gouttefangeas Cécile,Scholz Armin M.,Nueske Stefan,Maurer Andreas,Kneilling Manfred,Pichler Bernd J.,Sonanini Dominik,Rothbauer Ulrich
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.
Subject
Immunology,Immunology and Allergy