Neuropilin-2 and its role in the immune system in inflammatory and malignant diseases
Others and we have already shown that NRP2 is highly expressed in different subsets of immune cells of the myeloid and lymphoid lineage (Mol Immunol, 2017; Front Immunol, 2017). Indeed, NRP2 regulates macrophage efferocytosis in tumor associated macrophages in a pancreatic cancer model system (Cancer Res, 2018). Efferocytosis is a process, which allows macrophages to engulf necrotic cells material without eliciting an immune response.
Additionally, atherosclerosis associated macrophages express high levels of NRP2 as indicated by immunohistochemistry.
Aims of this project
We investigate the role of blocking NRP2 in macrophages to sensitize cancer entities that are not responsive to immune checkpoint inhibition (ICI) to ICI. NRP2 will be targeted using different approaches: Polymer nanoparticles loaded with short interfering RNA against NRP2 (in cooperation with Achim Aigner, Leipzig), orphan drugs that are screened for their ability to block NRP2 (in cooperation with the research group of Kaustubh Datta, University of Nebraska Medical Center, Omaha, NE, USA) as well as nanobodies targeting NRP2 loaded with radionuclides (in cooperation with the nanobody core facility at the University of Bonn and the nuclear medicine department at the University of Bonn Medical Center) and NRP2 blocking aptamers.
In addition, we investigate the role of NRP2 in atherosclerosis formation using different model systems.