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

Wagner TR
December 18, 2023
Front Immunol
https://pubmed.ncbi.nlm.nih.gov/38164132/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38164132/

Research summary

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.

Key outcome of the study

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

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.

TARGET:
Sirpa, Cd47
Signal-regulatory protein alpha, Integrin-associated protein

Keywords

Immunotherapy, Myeloid cells, SIRPα/CD47 checkpoint, Nanobody-based imaging, Cancer immunology

Technical specifications

Humanized Knockin mouse model, SIRPα/CD47 axis, Syngeneic tumor model, Nanobody development, PET imaging, Phagocytosis assays

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