Abstract 626: Personalized immunotherapeutic platform with evidence of clinical activity in glioblastoma (IGV-001) protects mice against other lethal solid tumor challenges

Abstract

Abstract Background: IGV-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 (BDC). We recently reported that IGV-001-treated newly diagnosed glioblastoma patients with methylated O6-methylguanine-DNA methyl-transferase promoter had a median progression free survival of 38.4 months compared with 8.3 months in historical standard-of-care-treated patients (P=0.0008). We have now found activity with the equivalent murine approach in multiple cancer models, highlighting the transformative potential of this immunotherapeutic platform beyond glioblastoma. Methodology: We utilized several murine models including the ID8-luciferase (-Luc) intraperitoneal ovarian cancer and Hepa1-6-Luc hepatocellular carcinoma orthotopic model. BDC containing saline or 1x106 IMV-001-treated tumor cells (hereon IOV-001 and IHV-001, respectively) were implanted in flanks of C57BL/6 mice and explanted 48 h later, as per glioblastoma clinical protocol. Tumor challenge for all models was conducted 28d after chamber implantation. Mice were monitored for survival and tumor growth, as determined by bioluminescence intensity. Cytokine assays and immunophenotyping were conducted. Results: 60% of IOV-001-treated mice were alive 58d post-tumor challenge, compared to only 19% of mice in the saline group (MST=37d, p=0.004). In the Hepa1-6 model, 50% of IHV-001-treated mice were alive by 100d post-tumor challenge (MST = 60.5d). In comparison, there were no survivors in the saline group beyond 28d (MST = 18d; p = 0.004). Most of the long-term survivors had undetectable tumor; a fraction showed some level of tumor burden which rose and fell, demonstrating immune control. Circulating IFNγ was significantly higher in IOV-001-treated mice compared to controls on 1d post-tumor challenge (p<0.001) and trended higher in those receiving IHV-001 14d after tumor challenge. Positive correlations were found between percentages of CD8+PD1+and CD4+TIM3+, and tumor burden in IOV-001-treated mice. On 14d, PD1+ expression in both CD4+ and CD8+ T cell subsets was significantly lower in surviving mice treated with IHV-001. Improved survival using this approach was also observed in the Pan02 orthotopic pancreatic model. Latest data will be presented. Conclusions: These data support the antitumor activity of this novel immunotherapeutic platform in multiple cancers beyond glioblastoma. Results suggest that efficacy is associated with a systemic immunological response, resulting in generation of Th1 antitumor cytotoxic T cells. Future studies are seeking to resolve the factors triggering good v. poor responses using phenotypic evaluation of T cell activation/exhaustion markers and Th1/Th2 cytokine production. Citation Format: Jenny Zilberberg, Amelia Zellander, Christopher Uhl, Christopher Cultrara, Kenneth kirby, Essam Elazaq, Charles B. Scott, David W. Andrews, Mark Exley. Personalized immunotherapeutic platform with evidence of clinical activity in glioblastoma (IGV-001) protects mice against other lethal solid tumor challenges [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 626.