P08.05.A VACCINATION AGAINST EXTRACELLULAR VIMENTIN RESHAPES THE TUMOR MICROENVIRONMENT AND IMPROVES SURVIVAL IN GLIOMA-BEARING MICE

Abstract BACKGROUND Glioblastoma is the most common malignant primary brain tumor in adults. The current standard of care, including surgical resection, radiotherapy and chemotherapy, slows the progression of the disease. Vimentin, an intermediate filament protein overexpressed by tumor endothelial cells, is secreted into the tumor microenvironment. Extracellular vimentin has pro-angiogenic and immunosuppressive properties, making it a potent target for cancer immunotherapy. MATERIAL AND METHODS We explored the anti-tumor activity of a conjugate vaccine to elicit a humoral immune response against extracellular vimentin. The vaccine or a control vaccine were injected four times followed by blood draws to assess antibody titers measured by ELISA. Following the vaccination phase, GL-261 or CT2A glioma cells were orthotopically injected into syngeneic mice. Survival was monitored and explanted tumors were analyzed for treatment-related effects. RESULTS The vaccination resulted in the induction of high anti-vimentin antibody titers that rose after each injection. Hyperimmune mice were injected with tumor cells and vimentin vaccine treatment inhibited tumor growth and extended the survival of glioma-bearing mice. Some animals experienced long-term survival. Tumors of vimentin vaccinated mice showed increased necrosis and apoptosis of tumor cells. In addition, an enhanced immune cell infiltration was observed, particularly of T cells and Fcγ receptor-positive cells. CONCLUSION Targeting extracellular vimentin via vaccination reshaped the tumor microenvironment and improved survival in glioma-bearing mice. This vaccination approach may represent a novel therapeutic option for the treatment of glioblastoma patients that warrants clinical investigation. The study is supported by the Eurostars-3 programme project OpSIS, #765.