P02.13.B MAGNETIC NAVIGATION OF IMMUNOBOTS TO ORTHOTOPIC EXPERIMENTAL GLIOMA MODULATES THE GLIOMA-ASSOCIATED MICROENVIRONMENT

Abstract BACKGROUND Glioblastomas are primary tumors of the central nervous system with a poor prognosis. They are characterized by deep infiltration into the surrounding brain parenchyma and an immunosuppressive tumor microenvironment, both of which pose significant challenges to current therapeutic strategies. Various cellular carriers—such as neural stem cells, mesenchymal stem cells, and bone marrow-derived hematopoietic progenitor cells (HPCs)—have been investigated for targeted delivery, and they indeed home to intracerebral gliomas even after intravenous administration. However, their migration cannot be externally controlled. Mobile microrobots are emerging tools capable of operating at the cellular scale and being steered wirelessly, potentially enabling access to otherwise inaccessible tumor regions. In this study, we explore a novel strategy utilizing such microrobots. MATERIAL AND METHODS We developed immunobots by loading autologous macrophages with Janus silica particles (~500 nm in diameter), which were half-coated with a 60 nm FePt nanofilm for magnetic guidance and functionalized with bacterial lipopolysaccharide (LPS) to induce an anti-tumorigenic macrophage phenotype. We evaluated their in vivo tolerability and therapeutic efficacy in the syngeneic, immunocompetent SMA560/VM/Dk glioma mouse model. Post-treatment effects were assessed by flow cytometry and immunohistochemistry. RESULTS Direct injection of immunobots into the striatum of VM/Dk mice was well tolerated, with no signs of autoinflammation. Intratumoral administration into orthotopic SMA560 gliomas led to modulation of the tumor microenvironment, including enhanced infiltration of T cells. Furthermore, intravenous administration of immunobots followed by magnetic guidance using a permanent magnet array successfully directed them to the tumor site and induced local immunomodulatory effects. CONCLUSION Our study demonstrates that magnetically guided microrobots based on autologous bone-marrow-derived macrophages enable the modulation of the glioma-associated tumor microenvironment.