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.
|Published - 19 okt 2023
|36th Annual Conference of the European Macrophage and Dendritic Cell Society - Ghent, Belgium
Duur: 18 okt 2023 → 20 okt 2023
|36th Annual Conference of the European Macrophage and Dendritic Cell Society
|Annual EMDS conference
|18/10/23 → 20/10/23