2009 Non-Invasive Multiplex ELISA Identifies Clinical Responders to Autologous Dendritic Cell Vaccine for Recurrent High-Grade Glioma in Phase 1 Clinical Trial

INTRODUCTION: Glioblastoma (GBM) is the most common primary malignant brain tumor with a dismal prognosis despite standard of care. Due to the immunosuppressive tumor microenvironment and intratumoral molecular heterogeneity, high grade gliomas are often resistant to immunotherapies. Recent studies have investigated the use of dendritic cell vaccines (DCV) derived from autologous tumor lysate for GBM to potentiate the local and systemic anti-tumor immune response with some success. METHODS: Using non-invasive multiplex immunophenotyping (48 cytokines for 38 total time points after vaccine administration), we evaluated longitudinal changes in tumoral radiographic progression and serum cytokine profile after surgical resection and DCV therapy. Our goal was to characterize differences in systemic immune response relative to radiographic progression (progressive disease vs. non-progressive disease: Complete Response, Partial Response, or Stable Disease). Using unbiased screening of serum cytokine profiles, we stratified clinical responders and non-responders using modified iRANO criteria. RESULTS: For this cohort, mean age was 57 years and median overall survival was 11 months. Using non-invasive multiplex ELISA we identified three immunosuppressive cytokines that correlated to treatment failure to DCV including RANTES (CCL5) (p<0.01), TNF- β (p<0.01), and MIP-1 β (p<0.05) at median follow up of 30 months. Additionally, we identified a significant difference in the global landscape of serum cytokines in recurrent high-grade gliomas that identified clinical responders to DCV. CONCLUSIONS: Overall, these results suggest a potential role for non-invasive immunophenotyping in predicting clinical responses to immunotherapy. Our phase 1 data suggests in certain patients autologous DCV may fundamentally alter the systemic immune response which can impact the state of disease progression.