ATIM-39. IMPROVED SURVIVAL NOTED IN GLIOBLASTOMA PATIENTS TREATED WITH ADJUVANT TLR-3 AGONIST IN SETTING OF AUTOLOGOUS LYSATE-PULSED DC VACCINATION

摘要

Despite advances in the understanding of glioblastoma multiforme (GBM) molecular biology, genomics, and tumor microenvironment, prognosis for patients diagnosed with this disease remains dismal with standard therapies. We and others have shown utility in dendritic cell (DC) vaccination as an active immunotherapeutic treatment for these patients. In this study, we evaluated the use of autologous tumor lysate puled DC vaccine with and without adjuvant toll-like receptor (TLR) agonists. TLRs are present on dendritic cells and serve to modulate immune responses. Twenty-three patients with WHO Grade III or IV glioma were treated with three intradermal injections of autologous tumor lysate-pulsed DC on days 0, 14, and 28 followed by adjuvant placebo treatment, resiquimod (TLR-7 agonist), or poly ICLC (TLR-3 agonist). Gene expression profiling, immunohistochemistry, and mass cytometry (cyTOF) were performed on patient tumors and peripheral blood mononuclear cells. Patients that received adjuvant poly ICLC had a significantly improved median survival of 54 months over placebo (11 months) and adjuvant resiquimod (17 months) groups. Within each treatment cohort, patients with Grade III tumors had increased overall survival over Grade IV tumors. Overall, patients with MGMT methylated tumors on pathology had a median survival of 57 months, while patients with MGMT unmethylated tumors had a median survival of 19 months. Our findings suggest that adjuvant TLR-3 agonist improves outcomes with autologous lysate-pulsed DC vaccine treatment.