Novel organoid platform for drug screening of patients with breast cancer.

Abstract

e13125 Background: Marketed methods are available for in vitro organoid growth for the purpose of translational science, evaluation of drug efficacy and patient treatment predictivity, but require needle biopsy of the tumor which is invasive to the patient. Non-invasive methods exist for isolating circulating tumor cells (CTC) from blood but require large volumes due to their low frequency (<1 in 105-106 PBMCs). Low CTC recovery limits the number of downstream analyses. To overcome these obstacles, Cellentia is introducing a novel in vitro system called R3CE (Rapid, Reproducible, Rare Cell Expansion), developed by AcroCyte Therapeutics Inc. (Taiwan), to the US market. The advantage of R3CE is that blood is used to generate viable representative cells of the patient’s tumor which can be expanded and banked, thus the number of characterization assays is flexible. The R3CE method allows for extensive drug screening within a rapid timeframe to inform patient treatment. This poster will show drug screening results on organoids derived from blood of breast cancer patients, and R3CE method transfer to Cellentia. Methods: For patient drug screening, 0.5 mL of peripheral blood was drawn from stage IV breast cancer patients. Cells were seeded onto proprietary plates, cultured for several days, passaged and screened for drug resistance or susceptibility to Cisplatin, Paclitaxel, 5-FU, Vinorelbine, and Gemcitabine by assessing the relative viability from luminescent measurements of drug treated organoids normalized to a mock control. For R3CE method transfer, frozen breast cancer organoids were thawed and seeded onto proprietary plates, grown for several days and used in the drug screen as described above. Results: Blood from five breast cancer patients (Patients A-E) were grown into organoids and used for screening drugs listed (Table). Relative viabilities were calculated. A threshold was set at 10% where relative viabilities above or below 10% showed the organoids were resistant (R) or susceptible (S) to killing by the drug candidate, respectively. The results of the R3CE drug test were compared to the clinical (Clin) outcome for each patient (clinical outcome is unknown (U) in some instances) and shown (Table). The drug test and the clinical outcome showed 100% concordance. Cellentia executed drug screening with the same drug panel utilizing frozen breast cancer organoids in the R3CE platform and demonstrated susceptibility in the drug screening. Conclusions: R3CE platform showed promising results as a personalized drug screening tool for breast cancer patients. Frozen breast cancer organoids for drug screening demonstrated successful method transfer to Cellentia. [Table: see text]