Background: Ovarian cancer is the most lethal of all gynecologic malignancies with a grim 5-year survival rate of ~47%. Mortality occurs in the setting of recurrent disease wherein the co-presentation of chemoresistance and carcinomatosis limits the value of standard of care. It is therefore imperative to develop approaches that can prevent recurrent ovarian cancer. Oncolytic viruses are genetically modified replication competent viruses that can selectively infect cancer cells to induce cell lysis and death. This approach has proven to be clinically safe making it a promising approach to complement standard of care. The objective of this study is to evaluate the efficacy of CARG-2020, a virus-like vesicles (VLV) delivering three immune-modulators including IL-12, IL-17 antagonist and shRNA-PD-L1 in preventing recurrent disease in a syngeneic mouse model of recurrent ovarian cancer.

Materials and Methods: In vitro: Triple knockout (TKO; p53LSL-R172H/Dicerflox/flox/Ptenflox/flox) mouse ovarian cancer cells were seeded in 96-well plates and treated with different doses of CARG-2020. Cell death was determined using the Incucyte imaging system. In vivo: TKO ovarian cancer cells stably expressing the mCherry fluorescent protein were injected i.p. in C57bl/6 mice (day 0) to mimic the establishment of recurrent disease. Treatment commenced on day 3 with the treatment group receiving three doses of 1x10^8 PFU of CARG-2020 given every other day (n=5). Control group received PBS (n=5). Both treatments were given i.p. Tumor growth was monitored by live imaging using mCherry fluorescence ROI area. Progression-free survival (PFS) was defined as the day ROI area reached 2,000.

Results: CARG-2020 (1x10^5 PFU) demonstrated cytolytic effect in vitro and induced 100% cell death within 24h. In vivo, CARG-2020 induced significant decrease in i.p. tumor growth (p = 0.0128) compared to PBS control. Treatment with CARG-2020 completely delayed the establishment of recurrent disease (PFS, p = 0.0003). Whereas PBS control group demonstrated median PFS of 20 days, mice in the CARG-2020 group remained disease-free until day 60.

Conclusion: CARG-2020 is able to prevent the establishment of recurrent disease in a syngeneic mouse model of recurrent ovarian cancer. Our results provide rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients.

Citation Format: Ayesha B. Alvero, Alexandra Fox, Bhaskara Madina, Valerian Nakaar, Timur Yarovinsky, Marie Krady, Bijan Almassian, Gil Mor. CARG-2020 artificial oncolytic virus delivering three immune-modulators prevents tumor recurrence in a syngeneic model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1150.