Abstract 4159: Ovarian cancer ex vivo 3D tumor cultures predict patient specific drug sensitivity
Authors: Grillet Fanny , Jariani Abbas , Overkamp Juul , Daszkiewicz Lidia , Yan Kuan , Price Leo S. , Vader Willemijn 
Published: September 2020

Introduction While systemic treatment has been quite static in the past decade in ovarian cancer, the challenge for the coming years is to stratify patients for optimal and new treatment strategies, such as targeting DNA damage response pathways, or immune modulation. Patient primary tumor from resections, biopsy or ascites can be cultured such that tumor heterogeneity and resident immune cells are preserved. These can be used to predict treatment response in patients or to test new cancer therapies. Here we present a high throughput short-term 3D ex-vivo culture platform combined with high content image-based analysis. This platform allows visualization and quantification of standard of care therapy and new drugs on fresh and cryopreserved patient derived ovarian cancer tumoroids.

Methods Patients with advanced primary or relapsing ovarian carcinoma are included in ongoing multi-center clinical trials in the Netherlands. Ovarian cancer derived tumoroids, freshly isolated or cryopreserved, are embedded in a protein-rich hydrogel and exposed to up to 20 drugs during a short term 3D culture. The automated high content imaging analysis platform measures a large panel of tumoroid morphological features, and responses such as tumor cell killing, growth arrest and local invasion are measured to define the response for each drug. In addition, clinical response data from the ongoing trials are collected to be correlated to clinical outcome of patients treated with systemic therapy.

Results We present results of drug sensitivity testing in patient-derived primary tumor cells of fresh and cryopreserved ascites and solid tumor. Patient-specific drug sensitivity is identified for up to 20 drugs including standard of care (e.g. carboplatin, paclitaxel) and novel treatment strategies (e.g. PARP inhibitors). Activity of immunomodulatory drugs were also monitored successfully in vitro. Accurate response evaluation demonstrates the feasibility of high-throughput drug screening on patient primary material within OcellO's platform. Our results show a high reproducibility in testing freshly isolated or cryopreserved material, highlighting the potential of a cryopreserved collection of patient derived primary material to test new drugs.

Conclusion OcellO's advanced 3D image analysis of patient primary material represents a rapid and biologically relevant approach to test various candidate compounds (e.g. antibodies, antibody-drug conjugates and small molecules) for ovarian cancer. The availability of drug response data combined with patient clinical data, including BRCA mutation and cytology/histology pathologist evaluation is expected to support drug discovery, improve the efficiency of clinical trials and establish predictive testing in the clinical setting.

Citation Format: Fanny Grillet, Abbas Jariani, Juul Overkamp, Lidia Daszkiewicz, Kuan Yan, Leo S. Price, Willemijn Vader. Ovarian cancer ex vivo 3D tumor cultures predict patient specific drug sensitivity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4159.