Combining RIAD and CAR T cell therapy

One of the major obstacles for current cancer immunotherapy is the immunosuppressive tumor microenvironment (TME) allowing tumor cells to escape immunosurveillance and anti-tumor immunity. CAR therapy has had very promising results towards non-solid tumors, but probably because of the TME the results in solid tumors have been limited. Two components of the TME, prostaglandin E2 and adenosine, targets the cAMP immunomodulating signaling pathway leading to retarded immune response. We have a mouse model where the negative immunomodulating cAMP signaling are blocked (RIAD mice). In this project, we want to combine the CAR treatment with T cells derived from the RIAD mice to investigate potential synergistic effects of RIAD and CAR treatment. We will challenge mice with a tumor model that harbors the target of our CAR and compare tumor growth with the treatment of CAR and RIAD-CAR. Our goal is thus to reveal potential synergistic anti-tumor immune effects of RIAD-CAR T cell treatment.