Image from left to right: Maarten Doornbos, Leo Price, Bram Herpers, Steven Kunnen.

What is CrownBio´s main focus?
Crown Biosciences Netherlands, formerly OcellO, is part of the global contract research organization (CRO) Crown Bioscience. Crown Bioscience is known for its extensive collection of PDX models that are used for in vivo testing. Since 2018 CrownBio also offers in vitro organoid services and upon acquisition of OcellO it is the only CRO with a commercial license to use HUB Organoid Technology. At CrownBio a growing, genetically characterized collection of >2500 PDX models, >300 PDX-derived organoid (PDXO) models and >200 Patient-derived organoid (PDO) models is available to test the effect of customer-provided compounds. CBNL facilitates the testing of compounds, compound combinations, antibodies, growth factors and antibody-drug-conjugates in 3D-cultured organoid models and is specialized in image-based analysis using the proprietary 3D image analysis platform Ominer® to quantify >500 morphological parameters to assess the effect of drug treatment on the 3D cultures of tumor and normal tissue-derived organoids and cell lines.

TransQST How has participating in TransQST impacted your company?
By being involved in the work package that focuses on intestinal toxicity, WP8, we were able to show that small intestinal organoids and colon organoids / enteroids behave differently in response to acute drug-induced toxicity. Because the treated organoids were provided as fixed material by the consortium partners, we had to invest time and effort in setting up methodologies that allow image acquisition and image analysis in different plate and well formats, requiring implementation of additional QC steps and development of additional readout methods to assess the tox effect of the drugs. Together with the modelling teams relevant features were identified that could be used to integrate additional organoid-derived measurements into the in silico models for predicting adverse drug effects. If indeed these models become more mainstream, we can thus provide organoid-based drug testing to deliver the required measurements to better predict drug toxicity.

What challenges has CrownBio faced across the project? What are your main achievements in TransQST?
The CrownBio image analysis techniques delivered additional insight into the mechanism of action of compounds in simulated adverse drug conditions. Effects on proliferation, cell death, cell polarity, nucleus-, lumen- and organoid morphologies were found to be correlating with other in vitro and also in vivo findings, both on cell and mRNA level. These findings were ultimately published in three separate publications.

What do you believe is the main contribution of TransQST in the field?
From an overall project perspective, TransQST facilitated a strengthening of the collaboration between different industries, academia, and service companies. Alignment of technology, sharing ideas and insights, implementation of novel methodologies and bringing together specialists from different domains has provided opportunities to allow for development of better and safer drugs. From a CrownBio / organoid technology perspective, the TransQST project has contributed to the integration of organoid technology in drug discovery, drug development and pre-clinical phases in a wider range of pharmaceutical companies.

Which TransQST outcome/s would you highlight? Why?
The recognition provided by the work performed under TransQST that PDO models can be used to assess and predict adverse drug effects in humans provides reason and opportunities to offer and generate additional patient-derived organoid models to the industry. The technology is in place, the incorporation of the technology and the readout outcomes are in development, and thus, as a CRO, CrownBio would like to see further strengthening of collaborations with the pharmaceutical industry.