ATIM-31. ALLOGENEIC TUMOR LYSATE / AUTOLOGOUS DENDRITIC CELL VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA: CLINICAL TRIAL MC1272

Abstract

INTRODUCTION: Dendritic cell (DC) vaccines for glioblastoma multiforme (GBM) have been promising in pre-clinical studies but clinical translation has been modest due to limitations imposed by source of antigens, poor DC maturation, and tumor-mediated immunosuppression. We report preliminary findings from a clinical trial combining a DC vaccine strategy that addresses these issues with standard therapy in newly diagnosed GBM. METHOD(S): Twenty adult patients with resected newly diagnosed GBM who had completed radiation / concurrent temozolomide were enrolled. DC's were generated in vitro from patients' CD14+ monocytes with an optimized technique for DC maturation. Vaccines were generated by pulsing autologous DC's with allogeneic tumor lysate from two patient-derived allogeneic human GBM cell cultures with defined tumor antigen expression. Patients received temozolomide plus vaccine for up to 6 cycles followed by vaccine alone for up to 6 cycles. RESULT(S): Patients enrolled were relatively enriched for poor prognostic factors (45% subtotal resection, 25% multifocal, 20% bilateral, 95% IDH wild type, 70% MGMT promotor unmethylated). Vaccine manufacture was successful (>= 15 doses of mature, > 70% CD83+ DC's) in all patients. Treatment has been well tolerated with only grade 1 - 2 toxicities (fever, rash, fatigue) potentially related to the vaccine. Increased circulating tumor-associated antigen-specific CD8 T-cells have been demonstrated post-vaccination with dextramer flow cytometry. Mean follow-up to date is 0.98 years (range 0.19 - 1.77 years); 16/20 patients are still alive. In the first 8 patients, median survival has not been reached with median follow-up 1.56 years. Post-vaccination tumor samples demonstrated moderate/marked inflammatory infiltrates in 5/7 biopsies. CONCLUSION(S): Autologous mature DC / allogeneic tumor lysate vaccines combined with temozolomide are safe, feasible, and generate tumor antigen-specific immune responses in a broad spectrum of newly diagnosed GBM patients. Initial survival data is promising, particularly in light of poor baseline prognostic factors in patients enrolled.