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

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.

Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy

“…Furthermore, T cells from mice receiving the murine version of IGV-001 produced IFNg in response to known tumor antigens from murine GL261 GBM cells [ 50 ]. Similar evidence of immunologic activity was seen in other mouse cancer models, including ovarian and urothelial cancers and hepatocellular carcinoma [ 50 , 60 , 61 ]. Together, these data strongly suggest that the use of this biologic-drug device product is a suitable approach to generate, contain, and release subcellular antigenic and immunogenic cargo to stimulate the immune system.…”

“…Studies conducted in syngeneic murine models support the use of the Goldspire ™ immunotherapy platform to treat a number of solid cancers beyond GBM. In the ID-8 murine ovarian carcinoma model (intraperitoneal, “metastatic-like”) [ 60 , 61 ], the Hepa1-6 murine hepatocellular carcinoma model (orthotopic) [ 50 , 62 ], and the MBT-2 murine bladder cancer model (orthotopic) [ 61 ], mice receiving a BDC prepared with the respective tumor cell line experienced significant prolongation of their mOS compared to mice implanted with saline-containing BDCs. These studies also demonstrated that the efficacy of this biologic-device combination product is associated with a systemic and durable immunological response, resulting in generation of Th1 antitumor cytotoxic T cells (unpublished data).…”