IMMU-23. Vaccination against extracellular vimentin boosts tumor immune cell infiltration and improves survival of glioma-bearing mice

Abstract Glioblastoma is the most common malignant primary brain tumor in adults. The current standard of care, including surgical resection, radiotherapy and chemotherapy, has only limited clinical efficacy and modestly slows disease progression. 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 suitable target for cancer immunotherapy. We explored the anti-tumor activity of a conjugate vaccine to elicit a humoral immune response against extracellular vimentin. In a preventive approach, the vaccine or a control vaccine was 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. In a therapeutic approach, GL-261 or CT2A cell implantation was followed by three injections of the vaccine or a control vaccine spaced by 10 days. Blood draws were conducted 5 days post-injection to assess anti-vimentin antibody response. In both approaches, mice were monitored for survival and explanted tumors were analyzed for treatment-related effects. The vaccination resulted in the induction of high anti-vimentin antibody titers that rose after each injection. Both vaccination approaches resulted in inhibited tumor growth and extended the survival of glioma-bearing mice. Some animals experienced long-term survival. Tumors of preventively 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. Targeting extracellular vimentin via vaccination reshaped the tumor microenvironment and improved survival of glioma-bearing mice. Our findings emphasize an important role of extracellular vimentin in the growth and progression of gliomas and provide a method targeting this vulnerability that may become a novel therapeutic option for the treatment of patients with glioblastoma.