This study focuses on the development of human SIRPα-specific nanobodies (Nbs) aimed at modulating the SIRPα/CD47 interaction and enabling in vivo imaging of myeloid cells. The research involves generating high-affinity Nbs to either block the SIRPα/CD47 checkpoint for enhanced phagocytosis or serve as imaging probes for non-invasive tracking of myeloid cell distribution.
The researchers identified nanobodies that specifically bind human SIRPα, with some blocking the SIRPα/CD47 interaction, thereby promoting macrophage-mediated phagocytosis of tumor cells. Additionally, a selected nanobody was labeled for PET imaging, enabling visualization of myeloid cell infiltration in tumors using the humanized mouse model.
Mouse Model: A humanized Knockin SIRPα/CD47 mouse model, where the extracellular domains of murine SIRPα and CD47 were replaced with their human counterparts. This model enables testing of nanobody interactions with human SIRPα/CD47 in a functional immune system. Cell Line: The study also used the MC38-hPD-L1-hCD47-LZ cell line, a murine colon adenocarcinoma model modified to express human PD-L1 and CD47, plus a luciferase-ZsGreen reporter, enabling syngeneic immune-oncology applications.
Immunotherapy, Myeloid cells, SIRPα/CD47 checkpoint, Nanobody-based imaging, Cancer immunology
Humanized Knockin mouse model, SIRPα/CD47 axis, Syngeneic tumor model, Nanobody development, PET imaging, Phagocytosis assays
From model design to experimental results
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Models with certified health status from professional breeders in US and Europe
