Led by the Francis Crick Institute and The Royal Marsden NHS Foundation Trust, the MANIFEST programme (Multiomic Analysis of Immunotherapy Features Evidencing Success and Toxicity), has been set up to evaluate the many barriers to the success of treatments based on using drugs to help the immune system fight cancer. This immunotherapy approach is a frontline treatment for some types of cancer like melanoma (a form of skin cancer), and long-term studies have shown that it can completely eradicate advanced disease for some patients.
However, the majority of people with cancer do not benefit, with many relapsing or experiencing significant side effects. Even in melanoma, where immunotherapy is most successful, only 50% respond. MANIFEST will aim to validate biomarkers - signs that suggest to doctors whether someone will or will not benefit from a given drug – and identify which are present in patients before they start immunotherapy, and to develop tests that can monitor them during treatment.
The initial testing will include 3000 patients who have already completed their treatment and then 3000 who are starting treatment across the UK for breast, bladder, kidney and skin cancer, with plans to include additional cancer types as the programme expands. Over four years, data will be collected from these patients, using procedures like blood tests, stool samples and tissue biopsies. The team will analyse different aspects of cancerous tumours, including their genetic makeup, where they are in relation to immune cells, and what chemical signals they are producing. They will also generate a profile of immune cells in each patient's bloodstream and analyse their gut microbiome.
Prof Kairbaan Hodivala-Dilke, Deputy Director of the Barts Cancer Institute, Queen Mary University of London, said: "We are very proud to be part of this exciting MRC MANIFEST UK consortium led by the Crick Institute. MRC MANIFEST leverages £9m from the Medical Research Council and the Office for Life Sciences, and £12.9m in matched funds from industry partners, this programme will involve thousands of patients treated with immunotherapy from across the UK. Integrating Queen Mary-initiated spatial omics analysis and forces from Tom Powels and Bernadette Szabados in bladder cancer, MANIFEST will discover and develop new biomarkers to optimise the use of the immunotherapies across multiple cancer types."
MANIFEST involves 16 academic institutions: The Francis Crick Institute; The Institute of Cancer Research, London; The University of Edinburgh; Cancer Research UK Manchester Institute; National Pathology Imaging Co-Operative; Genomics England; Hull York Medical School, University of York; The University of Cambridge; Queen Mary University of London; The University of St. Andrews; Queen's University Belfast; UCL; The University of Manchester; The University of Glasgow; Cancer Research UK Scotland Institute; Cancer Research UK National Biomarker Centre, and six NHS foundations trusts: The Royal Marsden NHS Foundation Trust; NHS Lothian; Cambridge University Hospitals NHS Foundation Trust; Barts Health NHS Trust; The Leeds Teaching Hospitals NHS Trust, and The Christie NHS Foundation Trust.
