Autologous tumor-lysate pulsed dendritic cell vaccination, together with the TLR-7 agonist 5% imiquimod, and serum pro- inflammatory cytokine levels in glioblastoma patients.

11021 Background: Standard therapy for glioblastoma, which includes surgery followed by radiation and concurrent chemotherapy, creates a low tumor burden environment that could be ideal for immunotherapeutic approaches. We conducted a Phase I study to assess the safety and immunologic responses of tumor lysate-pulsed dendritic cell (DC) therapy plus topical imiquimod, in combination with standard radio-chemotherapy.,Thirteen patients with newly diagnosed glioblastoma were immunized using autologous tumor lysate-pulsed DC at 2-week intervals, following completion of radio-chemotherapy. The primary clinical endpoint was 2-year survival. Patients without tumor progression subsequently received booster vaccinations combined with topical administration of the TLR-7 agonist, imiquimod. Immunologic responses to tumor antigens were monitored by tetramer staining and intracellular cytokine staining. Measurement of serum cytokine levels (T/T: IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10) was performed using cytometric bead arrays (CBA). Global gene expression profiling was also performed on pre-treatment tumor samples.,All immunizations were well tolerated, with only mild side effects attributable to the DC vaccination and imiquimod adjuvant. Increased levels of CD8 T cells reactive against tumor antigens, (e.g., gp100, TRP-2, her-2, survivin, and CMV antigens), were detected in 5 patients. CBA measurement of serum cytokine levels revealed small, but detectable levels of TNF-α following the initial DC vaccination. Robust increases in serum TNF-α and IL-6 were observed after booster vaccinations, temporally correlating with imiquimod administration. Clinically, 8 of the 13 patients have progressed, and 6 of those have died. The median PFS to date is 13.9 mos. and median OS is 33.8 mos. This compares favorably to the published literature, with a median PFS of 6.9 mos and OS of 14.6 mos.,This study demonstrates the safety and clinical/immunologic effects of an autologous tumor lysate-pulsed DC vaccine for patients with newly diagnosed glioblastoma. Serum TNFα responses may portend therapeutic anti-tumor immune responses to DC vaccination. [Table: see text].