A major new initiative involving Oxford experts aims to redefine human-based research models to improve understanding of disease and accelerate the development of new medicines.
The joint £15.9 million investment by the Medical Research Council (MRC), Wellcome Trust, and Innovate UK will enable the development of advanced, specific, and highly reproducible human in vitro models, with the aim of making them widely available to researchers in academia and industry.
In vitro models use isolated cells and tissues outside the living body and can take many forms, including stem-cell derived aggregates that display organ-like features on a smaller scale (organoids), tissue slices removed during surgery (called explant or ex vivo cultures); and organ-on-chips, small devices that use tiny channels to pass fluids through living cells, mimicking how organs work inside the body. The development of accurate and physiologically relevant in vitro models for studying disease biology and drug development aims to improve the translatability of research, while reducing reliance on animal models.
A coordinated network of five interdisciplinary teams will focus on the development of in vitro disease models of the liver, brain, cancer, pain and blood vessels.
Eric O’Neill, Professor of Cell and Molecular Biology, Department of Oncology, is part of the INTREPID project (IN vitro TumouR Explant models for evaluating cancer complexity and Patient Diversity) project, which aims to tackle the barriers associated with widespread adoption of live human tumour tissue explant models – to drive progress in their use in cancer research.
The INTREPID team brings together biologists, bioengineers, clinicians, computational scientists, and technologists from the University of Oxford, University of Leicester, Imperial College London, University College London, MRC Toxicology Unit Cambridge, and Medicines Discovery Catapult.
Existing preclinical models for cancer, including in vivo and multi-cellular models, cannot capture the full spectrum of cancer complexity needed to accurately predict a patient’s response to anti-cancer therapies. This means that preclinical results may not translate into successful clinical trials, and potential new therapies can take longer to reach patients.
Living samples taken directly from patients’ tumours offer a powerful and more predictive alternative. They maintain the natural structure and cell interactions found in real tumours, including the immune system and blood vessel systems, while also capturing patient diversity. This, in turn, should help scientists to predict which new therapies have the most potential more accurately.
“The value to patients of using human tissue as a model is that we will be able to test therapies on patients’ own tumours before they are prescribed a therapy. This will allow us to figure out what treatment is most likely to work for each patient and avoid using treatments likely to fail”, says Prof. Eric O’Neill, who is leading the effort in human tissue models at Oxford.
The project aims to:
- Accelerate the development, validation and implementation of the explant model system and reduce the reliance on in vivo models
- Improve our understanding of human cancer mechanisms and better support drug development
- Overcome limitations of current in vivo and in vitro cancer models, to more accurately reflect human disease and capture individual patient variation
“The wider advantage to the pharmaceutical industry is that we do not have to solely rely on animal research to test the safety and efficacy of treatments for humans, increasing the likelihood we can have greater success in clinical trials” - Eric O’Neill
Project lead, Catrin Pritchard, Professor of Cancer Biochemistry in the Division of Cancer Sciences at the University of Leicester, said:
“We are delighted to receive this award to deliver better outcomes for cancer patients. While a lot of the initial work will be on technical development of the explant platform, we will also be testing a range of advanced cancer therapies with the goal of designing personalised treatment strategies for individual patient benefit.”
A key ambition of the new investment is strategic coordination across the network of supported projects and to create connectivity with wider UK capabilities, including industry to join efforts and address common challenges in the field.
The funding was delivered in partnership with the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).