Elucidating immune suppressive mechanisms against CAR T therapy

Multiple myeloma (MM) is an incurable plasma cell cancer, localized in the bone marrow. Diverse immunotherapies are under evaluation to achieve
long-term remission in MM patients of which adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) has gained
popularity. CAR-T cell clinical studies overall show high objective response rates (up to 80%) in MM. However, a large number of patients relapses within a few years after reaching remission. Therefore, improved CAR-T cell strategies are urgently needed. We propose to study metabolic rewiring and immunosuppression in the tumor environment, which could hamper CAR-T cell therapy. We will gain novel insight into processes that need to be targeted in combination approaches to achieve better responses, which currently used agents such as immune checkpoint inhibitors fail to do. If successful, the project results can be translated to the clinic, leading to a novel treatment strategy for MM patients.