Abstract 4007: Building 3D ex vivo models as a powerful platform for anti-cancer drug and biomarker discovery

Abstract Patient-derived models have increasingly been adopted into target validation, lead-optimization and secondary screening campaigns to move translation ahead in drug discovery. While 2-dimentional cell line in vitro models continue to play a pivotal role in early screening studies, new advanced in 3D patient derived organoids (PDO) and patient derived xenograft organoids (PDX-O) technology have made it suitable to meet the rigor and reproducibility of traditional screening metrics. At Champions Oncology, we have built a successful pipeline of ex vivo models from pre-treated, metastatic, and genetically diverse cohorts across varied indications. PDX-derived cell cultures serve as (i) physiologically relevant high throughput platforms for early or clinical hypothesis testing, (ii) cellular systems to gain mechanistic and phenotypic insights into drug mode of action in 3D tumor microenvironment, and (iii) cost-effective translational bridge to well-informed in vivo studies. Ex vivo models have been widely established and characterized for non-small cell lung cancer (NSCLC), colorectal (CRC), and other epithelial tumor types. Indications such as renal cell carcinoma (RCC), Diffuse large B-cell lymphoma (DLBCL), gastric and bladder cancer, glioblastoma multiforme (GBM), prostate cancer, and sarcoma are less common and often a size-able cohort size rarely exists. In this poster, we showcase our recent efforts on the iterative media optimization process, growth kinetics, and morphology of models from these rare indications and characterization data that establish them front and center as valid preclinical screening tools. Through careful media formulation, the appropriate standard of care controls (SoC), and vigorous assay development criteria we show the versatility of these models for both efficacy and complex mechanistic readouts when probed with various modalities including antibody-drug conjugates (ADC) and anti-sense oligos (ASO). Our experience establishing 3D microstructures from various indications by iterative optimization of culture conditions is further validated by our comprehensive quality control (QC) procedures and deep molecular and pharmacological characterization. In summary, through a series of examples, we highlight the application of Champions TumorGraft3D Ex vivo models in enhancing the biological and clinical fidelity of novel modalities of drugs and/or novel drug combinations. Citation Format: Fu-Ju Chou, Annamaria Rapisarda, Mara Gilardi, Stefano Cairo, BanuPriya Sridharan. Building 3D ex vivo models as a powerful platform for anti-cancer drug and biomarker discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4007.