DescriptionNon-invasive imaging of different immune cells inside the tumor microenvironment could predict the patients’ response to immunotherapy1. Unfortunately, only a limited amount of good tracers to image immune cells are available in the clinic. In this study, we generated and characterized a cross-reactive nanobody-based immunotracer against CD163, a receptor that is specifically expressed on a subset of immunosuppressive tumor-associated macrophages (TAMs)2. This CD163-targeting immunotracer could be used for imaging of TAMs to predict immunotherapy response in cancer patients.
The CD163-targeting nanobody showed binding affinities in the low nanomolar range for both human and mouse CD163 proteins. Uptake of the lead nanobody-based immunotracer in macrophage-rich organs was demonstrated via μSPECT/CT imaging in naïve wild-type mice, while no uptake was shown in CD163-/- mice, supporting the specificity for CD163+ cells. Macrophage-specificity was proven by comparing untreated with macrophage-depleted mice. The signal of the immunotracer in liver and lymph nodes was significantly declined in macrophage-depleted mice validating the specific expression of CD163 on macrophages. μSPECT/CT imaging of LLC-OVA tumor-bearing mice, with subsequent flow cytometry analysis of the tumor, showed the ability of the immunotracer to target TAMs. The translation towards a PET tracer has been optimized and the binding of the PET tracer to CD163+ cells is currently being validated with different in vitro and in vivo experiments. The CD163-targeting nanobody is also being examined at the moment on competitive binding with ligands of the CD163 receptor. Further, the possibility of indirect T cell activation after binding of the nanobody to macrophages is being studied.
Altogether, we have developed a cross-reactive immunotracer that is specific for CD163+ macrophages and allows imaging of these immune cells in the tumor microenvironment. The radiolabeled nanobody-based immunotracer could be a promising clinical imaging agent to further study the role of CD163-expressing TAMs, predict immunotherapy responses and contribute to personalized medicine.
|19 sep 2023
|The Single-Domain Antibodies 2023 meeting: 3rd congress on single-domain antibodies
|Mate van erkenning