SRP-Onderzoekszwaartepunt: PACT: multi-omics Profiling of T cells to improve Adoptive Cell Therapy

The immune system can recognize cancer cells as these express unique proteins (antigens) that serve as an ‘ID’ for T cells, immune cells with their own unique proteins (receptors) that scan the ‘ID’ of cells. Each receptor can bind one antigen enabling cancer cell killing. This knowledge led to the use of T cells in cancer immunotherapy. Therapy with T cells that were manipulated in the lab to express CARs, improved man-made receptors, has merit in blood cancers. This encourages research into this therapy in difficult to treat cancer types in which T cells have to overcome several barriers imparted by cancer cells and their environment. We will focus on multiple myeloma (MM) and melanoma (refractory to other therapies). We have taken the first steps to make CARs with improved ability to bind antigens (e.g., CS1 in MM and B7-H3 in melanoma). To lower the therapy cost, research on how to deliver CARs to T cells in patients is ongoing. We believe that T cells should be armored to break the barriers present in the cancer environment to achieve the full potential of the therapy. This requires in-depth understanding of the T cells’ biology and how it is affected at various stages of disease. We will combine our expertise and state-of-the-art methods to study changes in T cells on the level of nucleic acids and metabolism. T cells will be isolated from cancer models (mouse and human) and patients. The obtained knowledge will be used to armor T cells, evaluating their ability to kill cancer cells in mouse and human cancer models. The novel insights that arise from this research will advance T-cell immunotherapies in cancer and other diseases, e.g., liver fibrosis or type 1 diabetes.