CAR T-cell therapy is a promising and innovative cancer treatment designed to use a patient's own immune cells to selectively find and destroy cancer cells. Although CAR T-cell therapy has greatly improved outcomes in hematologic malignancies, especially B-cell lymphomas, fewer than half of patients achieve lasting remissions. 

Our research team has studied a great number of tumor samples from patients treated with CAR T-cells to identify and better understand the underlying mechanisms of limited treatment efficacy. By using a multi-omics approach as well as engineered mouse models, we could identify several players of an immunosuppressive tumor microenvironment (TME), which is, amongst others, characterized by low oxygen levels (hypoxia). Moreover, we could demonstrate that the hypoxic TME represents a key barrier to efficient CAR T-cell treatment, which limits durable responses by driving T-cell dysfunction and immune evasion.

Building on our findings, the Boost-CAR project aims at developing a new type of CAR T-cell that possesses two key features to overcome the current limitations of CAR T-cell therapy: (1) Enhanced metabolic resilience and (2) unresponsiveness to immunosuppressive signals. The resulting CAR T-cells will be tested by using both patient samples and engineered mouse models that closely resemble human lymphoma. 

The results obtained in the course of this project will provide a molecular and immunological basis for a future clinical study aimed at enhanced therapeutic efficacy of CAR T-cells in patients with aggressive lymphoma. Going forward, this approach might also be used to treat solid tumors, such as lung cancer.