Organoids the missing link between cell lines and patients?

Organoids are a complex 3D model able to encompass the majority of the heterogeneity, the phenotypic and genotypic features of the original patient sample they are derived from. A platform has been setup in AstraZeneca to derive patient derived organoids (PDO) and patient derived xenograft organoids (PDXO). PDOs are derived from cancerous and matched normal lung resections from the Royal Papworth Hospital. These models will be shared with the Wellcome Sanger Institute to perform whole genome and RNA sequencing. Different organoids were used to set up all the protocols. The metabolic fingerprinting illustrated the metabolic differences between organoids and different tissues. This confirmed the heterogeneity of metabolite composition of each organoids in a same model. A screening pipeline has been established with two different analysis methods. An engineering protocol to genetically modify these organoids was created with a success rate of 60 to 80%. A live imaging protocol was set up to visualise the CAR-T or Antibody-drug conjugate (ADC) activity in co-culture with organoids. To mimic the tumour micro-environment (TME), embedded T-regs with the organoids were able to reduce the activity of CAR-Ts. Organoids are a relevant model to mimic the patient context and would be more efficient to increase the number of successful molecules in clinical assays. [Etienne De Braekeleer1, Sarah Consonni1, Romain Lara1, Lewis Chaytor2, Gemma Everitt3, Monica Patel3, Gregory Hamm6, Chen Qian4, James Pilling5, Stewart Jones6, Matthew Garnett7, Doris Rassl9, Robert Rintoul8, Jonathan Orme3, Ultan McDermott9, Benjamin Taylor1 AstraZeneca : (Discovery Sciences (1 Cell Biology & Immunology, 2 Cell Enginneering, 3 Cell Bank, 4 Imaging IT, 5 Functional Genomics), CPSS (6 Imaging Science) 9 Oncology Bioscience, Oncology TTD), 7 Wellcome Sanger Institute, 8 Royal Papworth Hospital]