218 Autologous glioblastoma tumor cells and an antisense oligonucleotide against insulin-like growth factor type 1 receptor protect against tumor challenge and generate T cell anti-tumor responses

BackgroundIGV-001 is a novel immunotherapy that combines irradiated, patient-derived glioblastoma tumor cells and an antisense oligonucleotide against insulin-like growth factor type 1 receptor (IMV-001) in biodiffusion chambers (0.1-micron pore size). We recently evaluated IGV-001 in patients with newly diagnosed glioblastoma.1 In a subgroup of IGV-001-treated, Stupp-eligible patients2 with methylated O6-methylguanine–DNA methyl-transferase (MGMT) promoter, median progression free survival was 38.4 months1 compared with 8.3 months in historical standard-of-care-treated patients (p=0.0008).2 We utilized the GL261-Luciferase (-Luc) glioblastoma orthotopic murine model and conducted in vitro immunological assays using patient-derived GBM tumor cells and matched peripheral blood mononuclear cells (PBMC) to unravel the potential mechanisms associated with the activity of IGV-001.MethodsBiodiffusion chambers containing phosphate-buffered saline (PBS) alone or IGV-001 prepared with 1x106 GL261-Luc cells were implanted in the flanks of C57BL/6 albino mice and explanted 48 hours later, as per the clinical protocol. GL261-Luc intracranial tumor challenge was conducted 28 days after chamber implantation. Mice were monitored for survival and tumor growth, as determine by bioluminescence intensity (BLI). For in vitro experiments, IGV-001 prepared with patient tumor cells were co-cultured with patient-derived PBMC to evaluate activated and memory T cell subsets and responses. To elucidate the immunostimulatory underpinnings of IGV-001, ATP release assay was conducted as a surrogate measure of immunogenic cell death.Results59% of IGV-001 treated mice were alive and continued to gain weight at the termination of the study, 58 days post–intracranial tumor challenge. In comparison, there were no survivors in the PBS group by day 24 (p