ATTRACT

In our state-of-the-art laboratories at CBmed, we have successfully established the isolation and cultivation of patient derived tumor cells (PDCs) and the downstream application of automated anti-cancer compound screening in a high throughput format in several cancer entities. The established and validated processes include the isolation of human tumor cells from primary patient material (tumor tissue), the short-term 3D cultivation for the formation of patient-derived tumor spheroids, and the ex vivo sensitivity screening process. With a focus on glioblastoma, a standardized workflow for isolation, cultivation and screening was set up and all quality-relevant workflows were validated (Figure 1). Additionally, an in-house data analysis pipeline was established. This pipeline reads raw data from high-throughput drug screening experiments, performs assay quality control, fits dose-response models, calculates the Area under the curve (AUC) and exports results to a report and visualizes the results in dose-response plots for individually optimized anticancer therapies. Between 2021 and 2023, more than 150 patient spheroids were screened against a tailored selection of 80 anti-cancer drugs, covering important pathways for targeted therapies (e.g., CDK4/6, PARP, PI3K/Akt/mTOR, EGFR, MET/ALK, VEGFR and others). Based on the efficacy of ex vivo drug sensitivity tests, a personalized medicine approach has been set up for patients with glioma.

The expertise accumulated thus far in ex vivo drug screening has led to our participation in the first randomized control clinical trial studying the efficacy of ex vivo drug screening in a subtype of glioblastoma. The trial titled Advanced brain Tumour TheRApy Clinical Trial (ATTRACT), has received funding via the Ludwig Boltzmann Gesellschaft. ATTRACT aims to establish proof-of-concept for functional precision medicine to match patients to the right drugs. This project is made possible via an interdisciplinary pan-Austrian consortium that leverages decades of experience accrued across neurooncological as well as basic and translational research centers. At the core of ATTRACT lies our innovative ex vivo drug screening platform that profiles the response of selected drugs on patient-derived tumor cells. The trial includes 5 sites across Austria (Graz, Vienna, Linz, St. Pölten and Innsbruck) with an accrual period of 48 months and a predefined interim analysis. In summary, the expertise we have built up at CBmed aligns with the work proposed in this study, aiming to improve treatment options for glioblastoma and medulloblastoma patients while reducing the use of animal experiments.