Journal Article

Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

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

2023

Overview

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 64 Cu-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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antibodies / Cancer immunotherapy / Chromatography / Flow cytometry / Growth factors / immune checkpoint inhibitor (ICI) / Immune checkpoint inhibitors / Immunology / Infiltration / Macrophages / Metastases / Myeloid cells / Nanobodies / nanobodies (Nbs) / PET imaging tracer / Phagocytosis / Positron emission tomography / SHPS-1 protein / SIRPalpha / theranostics / Tumors