With the increasing use of immunotherapy, it becomes clear that the immunosuppressive tumor microenvironment is an obstacle. Regulatory T cells (Treg) form an important component of this suppressive environment in tumors, but at the same time Treg are needed to ensure immune homeostasis in the rest of the body. Through the identification of IL-1R2 as a marker for tumor-infiltrating (ti)Treg, but not peripheral Treg, we aim to specifically target and disarm or deplete tiTreg. We will assess the importance of IL-1R2 in tiTreg functionality and will generate cross-reactive anti-mouse/human IL-1R2 Nanobodies as vehicles to either block or deplete IL-1R2high tiTreg in various mouse models. Based on our long-standing Nanobody experience, we will generate several Nanobody-formats (ADCCoptimized, biparatopic, bispecific, life-time extended) and will assess the best format, either as monotherapy or in combination with immune checkpoint blockade. Overall, this project will yield a novel therapy, targeting tumor-infiltrating Treg.
|Effective start/end date||1/03/21 → 1/03/25|
Flemish discipline codes
- Immunology not elsewhere classified
- Anti-Cancer Therapy
- tumor immunology
- Animal Model