HUB Organoids are Key to Advancing Personalized Cancer Therapies | Hub Organoid Technology | Corning

In 2008, Dr. Nick Barker at the Hans Clevers Laboratory identified that Lgr5 (leucine-rich repeat-containing G protein-coupled receptor 5) was a unique marker of adult stem cell populations. Since then, organoid research has advanced at a phenomenal rate. It was soon discovered that these cell-derived in vitro 3D organ models held remarkable promise for disease modeling, with the potential to help study cell behavior, tissue repair and drug response in an environment that mimics real-life clinical situations. A whole array of organs and tissues can now be recreated from stem cells, mimicking the genetics and cellular makeup of their source material to model human disease.

Since the Lgr5 discovery, the Clevers Lab has continued to develop new in vitro models to improve drug development and understanding of patient response, with the aim of translating the technology over to industry through its spin-out company, Hubrecht Organoid Technology (HUB). “We began to develop models via samples taken from the small intestine of a mouse,” says Boj. “We have now developed our processes using human tissue, producing liver, pancreas, breast, lung, and ovary organoids. We grow and send HUB Organoids to our international customers throughout the world, and we continue to maintain a small collection of animal models for our toxicology program.” 

As science advances, so does the number of treatment options available to patients, yet it remains difficult to predict which patient will be sensitive to which treatment. The ability to grow patient-derived organoids mimicking the biological features of a patient’s tissue makes it possible to test an array of drugs and observe how those cells react. For this reason, hospitals and pathology departments across Europe have chosen to collaborate with HUB, which now receives samples ranging from rectal and needle biopsies to tumor lesions. 

“As soon as we receive a sample from a hospital, the sample is processed. My team dissociates the cells and isolates the epithelial cells,” says Boj. “Once isolated, the cells are transferred onto a culture plate, and in a matter of days, we can physically observe the organoids. Depending on the tissue type, the sample quantity and quality and the disease model, we can generate enough organoids to create a master cell biobank within weeks of receiving a patient sample.” While intestinal models, for example, usually take two to three weeks, other models can take up to 12 weeks.

“After the identification of a tumor, we need to be able to quickly generate organoids and perform a screen,” continues Boj. “Doctors need to treat the patient with the most effective treatment between four and six weeks after diagnosis.” Despite the short deadlines, the team at HUB has succeeded in meeting this target for some cancers, but not all. “Another significant challenge of ours is to predict patient response,” Boj continues. “Genetics does help identify certain treatments based on genetic landscape and mutation presence, however, the same mutation present in another patient does not necessarily mean that you can predict patient response. We now observe organoids from a range of patients suffering from the same mutations and we carefully observe the difference in response.’’