Immunomodulatory properties of Smac mimetic on the primary tumor and after tumor resection on preclinical mouse and human models in glioblastoma – MEGA01

The establishment of an immunocompetent microenvironment represents a major therapeutic challenge in the treatment of glioblastoma. These brain tumors are one of the most angiogenic and immunosuppressive tumors with limited therapeutic options. To increase treatment efficiency, we need molecules targeting cancer cells but also vessels and immune cells. We identified the Smac mimetic GDC-0152 which can kill tumor cells, normalize tumor vessels, and modify the immune landscape. The objectives of the MEGA01 project are to dissect the immunomodulatory properties of GDC-0152 throughout glioblastoma progression, to investigate whether the tumor resection will modify these immunomodulatory properties, and to validate our mouse data to human by developing a suitable preclinical human glioblastoma model for translational to the clinic. To study glioblastoma-induced immune response, we will combine the use of multicolor mice, intravital two-photon imaging, brain clarification and mass cytometry.