Modulation of T cell and macrophage tumor infiltration by the TLR9 agonist lefitolimod in a murine model of colorectal cancer.

687Background: The use of TLR9 agonists for immunotherapeutic approaches is supported by preclinical and ongoing clinical studies. Lefitolimod, a covalently-closed dumbbell-shaped DNA construct, is an immune surveillance reactivator which broadly activates cells of the innate and adaptive immune system. The conversion of non-immunogenic (cold) tumors into immunogenic (hot) tumors, characterized by their T-cell infiltration, is a pre-requisite for response to immunotherapies. By its mode-of-action lefitolimod likely provides the necessary signals for activation of immune cells and their differentiation into anti-tumor effector cells as well as their recruitment to the tumor microenvironment (TME). Methods: To support the further clinical development of lefitolimod in mCRC, the syngeneic colon carcinoma model CT26 was used to evaluate anti-tumoral efficacy of lefitolimod and its modulation of the TME. The phenotype of T cells and macrophages present within tumor-infiltrating immune cells were analyzed by fl...