Introduction/Background The immune system has proven to be involved in ovarian cancer (OC) disease, yet, clinical immunotherapeutic trials have not resulted in convincing successes. Innate immunosuppression is currently left untackled. Anti-TIM3 (T-cell immunoglobulin and mucin-domain containing-3) has a potential advantage for OC immunotherapy, since it can manipulate the function of innate (macrophages and dendritic cells) and adaptive (CD4+, CD8+ and regulatory T-cells) immune cells.

Methodology Female C57BL/6 mice were inoculated intraperitoneally (IP) with 5x10^6 ID8-fLuc OC cells. Treatment was initiated 20 days post inoculation and consisted of carboplatinum-paclitaxel (C/P) chemotherapy (100mg/kg and 10mg/kg respectively) through a single IP injection with or without biweekly IP administration of anti-TIM3 (InVivoMAb anti-mouse TIM3 (CD366)) (350µg/injection) for three or four weeks in different schedules. Survival was recorded using predefined humane endpoint criteria. The immune system was analysed at predefined time-points using fluorescence activated cell sorting on peritoneal washings.

Results Anti-TIM3 monotherapy did not induce changes in disease progression. Moreover, addition of C/P to anti-TIM3 treatment did not prolong the survival of OC bearing mice compared to mice treated with C/P alone. However, adapting the sequence from sequential administration, with first C/P and one week later anti-TIM3 administration, to simultaneous administration of both treatments improved the survival of tumor bearing mice (p=0.0287). From an immunological perspective, we observed a significant reduction in the percentages of regulatory T-cells in the cohort receiving the sequential combination treatment compared to the mice receiving the simultaneous treatment. Additionally, prolonging the anti-TIM3 treatment duration from three to four weeks in combination with simultaneous C/P resulted in significantly increased survival (p=0.0151).

Conclusion Overall, we show that anti-TIM3 does not improve the survival of OC-bearing mice in monotherapy or in combination with C/P compared to C/P alone, however our results highlight the importance of the order and duration when combining immunotherapeutic treatments with chemotherapy.

Disclosures AC is a contracted researcher for Oncoinvent AS and Novocure and a consultant for Sotio a.s. and Epics Therapeutics SA.