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Biotherapies, Cellular Therapies, and Immunotherapies

(P-BT-2) Preventing Disease Progression in an Ovarian Cancer Mouse Model

Sunday, October 20, 2024
12:00 PM – 1:00 PM  
Background/Case Studies: This study evaluated a novel cell-based immunotherapy protocol using Riboflavin and UV light-inactivated tumor cells to trigger an immune response and prevent tumor progression in a mouse model of ovarian cancer. The inactivated cells contain autologous tumor epitopes and neo-antigens that can interact with the immune system to stimulate tumor-neutralizing immune responses. This interaction, however, is likely to be highly regulated. Therefore, we aimed to disrupt this regulation by altering the immune system through the inclusion of a TLR9 agonist, CpG1018—an unmethylated cytosine-phosphate-guanine oligodeoxynucleotide—as an adjuvant. This study examined if treatment with a combination of Riboflavin and UV-inactivated cells with an adjuvant could boost the immune response by stimulating Th1-type immune responses, potentially paving the way for more effective ovarian cancer treatments.

Study

Design/Methods:
We designed the study to use the ID8-Luc murine ovarian intraperitoneal (IP) dissemination allograft model. C57BL/6 mice were IP inoculated to simulate disseminated disease. The primary endpoint was time to peri-morbidity (survival), and bioluminescent imaging (BLI) was used to monitor the progression of the disease. The groups analyzed were as follows: A placebo control group receiving CpG1018 only (group 1) and groups 2, 3, and 4 receiving three different concentrations of Riboflavin and UV-inactivated cells + CpG1018. 


Results/Findings:

Whole-body BLI measurements were performed once weekly for 56 days. The mean values for BLI at Day 22 post-tumor implantation and survival per group are shown in Table 1, below:


Conclusions:
Riboflavin and UV inactivated cells with CpG1018, across all dose levels (groups 2, 3, and 4), consistently outperformed the Placebo control (group 1) with adjuvant alone, demonstrating lower mean BLI values throughout the study. Furthermore, there was no statistically significant difference in mean BLI values between the combination of Riboflavin and UV inactivated cells with adjuvant based on the number of inactivated cells in the formulation. Survival was assessed for all groups against the Placebo control group (group 1). Furthermore, all treatment groups (groups 2-4) outperformed the Placebo control, resulting in a statistically significant increase in survival. All Long-Rank test values were p< 0.0001.