Immunotherapy of cancer has witnessed a clinical breakthrough since the discovery and successful application of so-called immune checkpoint blockers. These are antibodies that block the function of immune checkpoint molecules, which negatively regulate the function of cytotoxic T lymphocytes (CTLs). Hence, immune checkpoint blockers boost the activity of anti-tumor CTLs, resulting in enhanced cancer cell killing.
Though the effect of these new therapies is spectacular in responding patients, the majority of the patients is still refractory to this treatment. One possible explanation is the redundancy of multiple immune checkpoint molecules. We identified VSIG4 as a molecule with T-cell suppressive
capacities (i.e. an immune checkpoint molecule) that is highly upregulated on tumor-infiltrating macrophages, in particular those macrophages that promote tumor growth. A VSIG4 deficiency results in a reduced tumor growth in multiple tumor models, suggesting that the blockade of this molecule could be a novel therapeutic option.
In this project, we will investigate via which mechanism(s) VSIG4 stimulates tumor growth, and we will generate VSIG4 blocking Nanobodies to assess their potency as monotherapy, or in combination with other immune checkpoint blockers or chemotherapy. If successful, this project may propose a novel class of cancer therapeutic agents: the VSIG4 blockers.
Effective start/end date1/01/1931/12/20

    Research areas

  • cancer therapy

    Flemish discipline codes

  • Cancer therapy

ID: 43822409