Abstract 3718: ID8-Luc syngeneic ovarian cancer model for preclinical evaluation of immunomodulatory molecules
Authors: Urs Sumithra , Barnes Sheri , Roys Stacey , Franklin Maryland R. 
Published: August 2019

Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate of over 14,000 deaths annually in the US. Although ~ 80% of OC patients initially go into remission after 1st line treatment (surgery and chemotherapy), more than 60% relapse within 16-18 months. Low neoantigen burden and the immunologically “cold” nature of OC makes it a challenging malignancy. Therefore, novel methods such as immunotherapy and/or combined therapies are essential to improve clinical outcome of patients. This work evaluated the ID8-Luc murine ovarian carcinoma model to determine sensitivity to immunomodulatory agents. C57BL/6 albino mice implanted intraperitoneally with ID8-Luc cells were evaluated for growth and sensitivity to checkpoint inhibitors anti-PD-1, anti-PD-L1, anti-CTLA-4 and the chemotherapy agent paclitaxel. Disease progression was monitored weekly by in vivo bioluminescence imaging (BLI). Baseline immune profile of the model was determined by collecting ascites from untreated mice and analyzed with panels for myeloid and lymphoid cell populations by flow cytometry. ID8-Luc cells successfully established tumors with 7-8 days doubling time, as determined by BLI, and a median overall survival time of ~ 40-50 days. Formation of ascites resulted in weight gain and extended abdomen at advanced disease state. Necropsy showed solid tumor nodules within the peritoneal cavity including involvement of pancreas, liver, spleen and abdominal wall. Baseline immune profiling of ascites indicated presence of B cells (23%), granulocytic myeloid derived suppressor cells (G-MDSCs; 15%), TAMs (25%) and a low percentage of T cells (3-4%). This was suggestive of a possibly “cold” tumor model. Paclitaxel is a front-line chemotherapy option in OC. We find that the ID8-Luc model has 60% tumor free survivors (TFS) following treatment. To determine how this model responds to immune checkpoint inhibition we tested response to anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies. Treatment was initiated at either 7 (early) or 14 (late) days post tumor cell implant and we found that the overall response varied depending on the timing of treatment initiation. Early treatment with either anti-PD-1 or anti-PD-L1 resulted in complete regression of tumors (100% TFS) while the model was refractory to anti-CTLA-4 treatment. Late treatment initiation of anti-PD-1 or anti-PD-L1 resulted in an “all or nothing” response (40% complete response and 60% non-response). In addition, reducing the antibody dose from 10mg/kg to 5mg/kg did not make a material impact on the anti-tumor activity of these agents in the late treatment regimen. New models to further the preclinical testing of agents for OC is vital. This work characterizes the baseline immune profile of the murine ID8-Luc model along with response to checkpoint inhibitors to enable the rational design of combination strategies in the preclinical setting.

Citation Format: Sumithra Urs, Sheri Barnes, Stacey Roys, Maryland R. Franklin. ID8-Luc syngeneic ovarian cancer model for preclinical evaluation of immunomodulatory molecules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3718.