Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells.
Front Immunol
; 14: 1264179, 2023.
Article
in En
| MEDLINE
| ID: mdl-38164132
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Single-Domain Antibodies
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Front Immunol
Year:
2023
Type:
Article
Affiliation country:
Germany