The Humane Research Trust is funding a research project at Sheffield Hallam University which will repurpose surgical waste tissue to develop fully humanised models for cancer immunotherapy testing. This innovative approach aims to replace animal testing and animal-derived products with patient-derived alternatives, paving the way for more ethical and effective cancer treatments.
Bowel cancer, or colorectal cancer, is the third most common cancer worldwide and the second leading cause of cancer-related deaths in the UK. Despite advances in surgery and chemotherapy, up to 50% of patients experience disease recurrence, highlighting the urgent need for better therapies.
Immunotherapy - treatments that retrain the patient’s own immune system to attack cancer cells - offers enormous promise. However, only 15-20% of bowel cancer patients respond to current immunotherapies. This low success rate is largely due to the complexity of the tumour microenvironment.
The tumour microenvironment includes the extracellular matrix, a dense network of proteins that becomes stiff and fibrotic in cancer. These changes create physical and biochemical barriers that block immune cells from reaching tumours and allow cancer cells to evade detection. Therefore, understanding and overcoming these barriers is critical to improving immunotherapy success.
Modelling the complexity of bowel cancer in the laboratory is difficult. Scientists often resort to inducing tumours in mice to test treatments. However, this approach is extremely inefficient; 95% of cancer drugs that work in mice fail in human trials.
Alternatives such as organoids (mini tumours grown from a patient’s cells) and cancer-on-a-chip models show promise, but these often rely on animal-derived products like calf serum or mouse tumour components.
To improve bowel cancer treatment, human models of the disease are urgently needed. Not only would this reduce the number of animals sacrificed, but it would also ensure that research is based on human biology, producing results that can actually help patients.
“Mice have different physiology to humans yet are used for immunotherapy testing due to the difficulty of studying immune, cancer, and tissue interactions,” explains Dr Nick Peake, Senior Lecturer in Biomedical Sciences at Sheffield Hallam University. “Our team believes that human tissue is the most realistic cellular, biochemical and biomechanical environment for modelling human disease.”
The Humane Research Trust is funding Dr Peake’s laboratory at Sheffield Hallam University to develop a new way to improve bowel cancer treatment. Through a collaboration with Sheffield Teaching Hospitals NHS Foundation Trust, the researchers will repurpose surgical waste tissue and blood samples from bowel cancer patients to create fully humanised, immunocompetent models.
Importantly, their model will integrate various cell types - including cancer cells, fibroblasts, and immune cells - all within a human extracellular matrix scaffold, accurately replicating the tumour microenvironment. This means they can observe how a patient’s immune system responds to their cancer cells, and how the tissue structure acts as a barrier to cancer immunotherapy.
They will then test drugs that target both the immune cells and the surrounding tissue barriers. This will provide proof-of-concept for a platform that can test cutting-edge immunotherapies and tissue-targeting drugs in conditions that truly reflect human biology. Additionally, while the project will focus on bowel cancer, the methods could be applied to many other cancers.
“This project aims to turn surgical waste into a resource - enabling better understanding of human disease by using human tissue,” explains Dr Peake. “By developing a platform based on human tissue and cells, this project could help to reduce reliance on up to 165,000 mice used annually in UK cancer research.”
Dr Nick Peake
Principal investigator
Dr Nick Peake is a Senior Lecturer in Biomedical Sciences at Sheffield Hallam University. His work is focused on the relationship between the extracellular matrix that provides structural support to cellular tissues, and the processes that contribute to disease. His current research uses 3D cell culture models of colorectal cancer to investigate its progression and barriers to treatment.
