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Preclinical disease models are essential for the development of novel therapies and help better understand the molecular processes that are deregulated by CFTR mutations. In recent years, a novel technology to generate patient specific in vitro cultures, organoids derived from adult stem cells, has gained widespread interest for the development of new therapies and as a predictive diagnostic tool. After we developed the HUB Organoid Technology, we established a large biobank of over 500 CF patient-derived rectal organoids. In this biobank, both common and rare CFTR mutations are captured. Several recently developed CFTR molecular modulators have been screened in HUB Organoids of the CF organoid biobank. The Forskolin-Induced Swelling (FIS) assay measures CFTR activity in a real time manner. Here we report the application of the HUB Organoid biobank and the FIS assay for drug development projects. CFTR activity was restored with correctors and potentiators or read-through agents in patient-derived organoids with multiple CFTR mutations. Furthermore, we report on the reproducibility and stability of the assay, which makes patient-derived HUB Organoids a feasible means to test the response of existing and developmental drugs for individual patients.

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On the Latest in Organoid Technology—Robert Vries, PhD—Hubrecht Organoid Technology (HUB)

On the Latest in Organoid Technology—Robert Vries, PhD—Hubrecht Organoid Technology (HUB)

BioTechniques Digital Editor, Tristan Free, speaks to Rob Vries, CEO of HUB. We explore HUB's use of organoids for drug development and to further study and improve the clinical treatments of diseases such as cystic fibrosis. After an analysis of the advantages of HUB Organoids over 2D cell cultures and animal models, we dive into how HUB Organoids are being used to investigate COVID-19.

Talking Techniques | Rob Vries on organoids for drug discovery and the study of COVID-19

Our Chief Research Officer Dr. Sylvia Boj discusses the advantages of HUB Organoids and how these 3D tissue cultures have enormous potential to revolutionize how we treat patients and predict therapeutic response.

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Our Chief Research Officer Dr. Sylvia Boj discusses a recent paper that used patient-derived organoids as a test case for a new CRISPR technique and talks about the impact this technology could have in the development of organoids for regenerative medicine. Additionally, she discusses future developments in organoids, and their involvement in drug discovery and cancer research.

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One of the main challenges of conventional cancer therapy is using a “one-size-fits-all” treatment for all patients. Most of patients who undergo drug treatment suffer from side effects and little or no clinical improvement. Patient derived organoid (PDO)s are a disruptive innovation that creates the possibility to establish predictive models for individualized cancer-based treatment strategy. HUB has successfully established organoid culture methods to generate organoid biobanks from healthy and cancer patients with high quality and reproducibility. HUB Organoids recapitulate complex characteristics of the original parental tissue including molecular heterogeneity and cellular composition of their tissue counterparts. Cancer immunotherapy has revolutionized the treatment options for cancer patients. However, given the heterogeneity between and within tumors and various immune system evasion mechanisms, treatment does not work for all patients. Developing organoid-immune cell co-culture assays might recapitulate this diversity and provide a (pre)clinical predictive model for tumor responsiveness towards immune cell therapy. At HUB, we have successfully developed image-based analysis to visualize Immuno-Oncology (IO) interactions as well as measurements of immune cell cytotoxicity against tumor organoids for colorectal, lung and pancreatic cancers. Currently, we are developing a reproducible and quantitative co-culture model of tumor derived organoids and immune cells for IO drug screening assays. These co-culture models will serve as a platform for preclinical research, aid in clinical development and could finally become a diagnostic tool to predict individual patient response to therapy.

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HUB has developed 3D culture systems to establish and expand human epithelial tissue from a variety of organs both healthy and diseased, such as cancer. HUB Organoid Technology is based on work of Hans Clevers that identified adult stem cells in many human tissues including, but not limited to intestine, liver, pancreas, breast, and lung. Organoid cultures have long term expansion capacity, genetically and phenotypically stable and retain biological and functional properties of the original tissue. HUB Organoids recapitulate the original tissue response to external stimuli and therefore provide a unique and robust ex-vivo model for drug development, diagnostics and patient drug response stratification for personalized medicine. Currently HUB is developing co-culture assays to combine Organoid Technology with immune cells for immune oncology-based treatments and immunotherapeutic compounds for inflammatory and autoimmune diseases. HUB has built a comprehensive living organoid biobank of well-characterized HUB Organoids from different healthy, disease and cancerous tissues of multiple organs. With the living organoid biobank and the Organoid Technology, HUB has a unique platform to develop assays and collaborates with clinical, pharmaceutical and biotech industry for personalized medicine, preclinical drug discovery, efficacy validation and toxicity.

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Take a look at the heart of Hubrecht Organoid Technology and watch the video with our Chief Research Officer Sylvia F Boj, in which she talks about HUB and our work with organoids for personalized medicine.