Samenvatting

Non-invasive imaging of different immune cells inside the tumor microenvironment could predict the patients’ response to immunotherapy. Unfortunately, only a limited amount of good immunotracers to image immune cells are available in the clinic. In this study, we generated and characterized a cross-reactive nanobody (Nb) against the marker CD163, a receptor that is specifically expressed on a subset of immunosuppressive tumor-associated macrophages (TAMs). The anti-CD163 Nb shows affinities in the low nanomolar range for both human and mouse CD163 proteins. An in vivo biodistribution experiment with pinhole μSPECT/CT demonstrated uptake of the lead Nb-based immunotracer in macrophage-rich organs in naïve WT mice, and no uptake in CD163-/- mice, supporting specificity for CD163+ cells. Macrophage-specificity is proven by comparing untreated and macrophage-depleted mice (using the CSF1R inhibitor PLX3397). Untreated mice show high uptake of the immunotracer in macrophage-rich organs and its signal in liver and lymph nodes significantly declines in macrophage-depleted mice, validating the specific expression of CD163 on macrophages. LLC-OVA tumor-bearing mice show Nb uptake in the center of the tumor on μSPECT/CT, correlating with high CD163 expression levels on TAMs. Translation towards a PET tracer has been optimized and validated with 68Ga-labeling. When the predictive value of CD163-expressing TAMs is established, this CD163-targeting immunotracer could be a promising clinical imaging agent to predict immunotherapy response and contribute to personalized medicine.
Originele taal-2English
StatusPublished - 19 okt 2023
Evenement36th Annual Conference of the European Macrophage and Dendritic Cell Society - Ghent, Belgium
Duur: 18 okt 202320 okt 2023

Conference

Conference36th Annual Conference of the European Macrophage and Dendritic Cell Society
Verkorte titelAnnual EMDS conference
Land/RegioBelgium
StadGhent
Periode18/10/2320/10/23

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