Immunotherapy, immune modulation, cytokine, cancer resistance, tumor escape
We are interested in the function of cytokines in the immune system during health and disease. We study how cytokines coordinate immune homeostasis and responses, and how they stimulate various immune cells in vitro and in different models of cancer, inflammatory and autoimmune disease, as well as allograft rejection. We generate and characterize natural versus modified cytokine formulations, including cytokine-antibody complexes, in order to better understand cytokine biology and improve cytokine-directed immunotherapy.
Our research focuses on the study of cytokines in the immune system to better understand their biology and improve cytokine-mediated immunotherapy. A well-studied example is interleukin-2 (IL-2). Due to its ability to stimulate anti-tumor immune cells, high-dose IL-2 treatment was the first approved immunotherapy used in patients with metastatic cancer. However, the high doses of IL-2 necessary to achieve clinical response lead to severe adverse events and the stimulation of immunosuppressive cells. We were able to address these shortcomings of IL-2 immunotherapy with the generation and study of particular anti-IL-2 monoclonal antibodies. One of these antibodies termed NARA1 directs human IL-2 preferentially to effector immune cells that show anti-tumor acitivities, such as CD8+ T cells and natural killer cells, whereas stimulation of immunosuppressive regulatory T cells and unwanted adverse effects are reduced. IL-2/NARA1 complexes show alone or in combination with other anti-cancer approaches strong anti-tumor effects in several preclinical tumor models.Publications