1071 Autologous tumor cell immunotherapeutic platform induces stress-correlated immunogenic cell death leading to immune activation within the draining lymph nodes

Abstract

Background Imvax is developing a novel personalized immunotherapeutic platform combining irradiated patient-derived tumor cells and insulin-like growth factor type-1 receptor antisense oligonucleotide (IMV-001) in biodiffusion chambers (BDC; 0.1-micron pores). The combination product IGV-001 was recently evaluated in a newly diagnosed glioblastoma (GBM) phase 1b clinical trial 1 . Median overall survival of highest exposure IGV-001-treated ‘ Stupp-eligible patients (n=10) was 38.2 months compared with 16.2 months in recent standard-of-care-treated [NCT02507583]. Imvax also reported anti-tumor activity of IGV-001 in the GL261-luc GBM murine model 3 . Here, we show that IGV-001 is associated with activation of stress-related pathways and the release of immunogenic cell death (ICD) molecules capable of stimulating myeloid and T cell subsets with potential anti-tumor activity in the draining lymph nodes (DLN) proximal to the BDCs. Methods GL261-IGV-001 was formulated and BDCs were incubated at 37 ° C and 5% CO2 for 48h. Supernatants were analyzed for extracellular ATP (eATP) and high mobility group box 1 (HMGB1) protein as indicators of ICD, along with flow cytometric analysis of viability, surface calreticulin exposure, and reactive oxygen species (ROS). Stress-related pathways