A nationwide team of universities, hospitals and industry led by the Francis Crick Institute and The Royal Marsden NHS Foundation Trust, have launched a new platform to understand immunotherapy response and side effects in cancer, with the National Pathology Imaging Co-operative playing a critical role.
Funded by £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.
The new UK-wide programme, titled MANIFEST (Multiomic Analysis of Immunotherapy Features Evidencing Success and Toxicity), has been set up to evaluate the many barriers to the success of immunotherapy. These include a lack of testable and usable biomarkers, signs that suggest to doctors whether someone will or will not benefit from a given drug. Identifying these biomarkers could help to select patients most likely to benefit, but also reveal avenues for new treatments, like vaccines and cell therapies.
Leeds Teaching Hospitals NHS Trust (LTHT), through the National Pathology Imaging Co-operative (NPIC), is playing a critical role in the delivery of the MANIFEST programme. NPIC will provide national pathology infrastructure and domain expertise for the programme.
As part of the MANIFEST programme, NPIC will help develop a national platform that integrates digital pathology and multiomic data. This platform will support researchers in identifying critical biomarkers, enhancing the ability to tailor immunotherapy treatments to individual cancer patients. NPIC’s advanced digital pathology imaging technology will play a key role in storing and analysing multiomic data.
Drugs that help the immune system fight cancer, collectively known as immunotherapy, are a frontline treatment for some types of cancer like melanoma. Long-term studies have shown that it can completely eradicate advanced disease for some patients. But 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 which biomarkers are present in patients before they start immunotherapy, and to develop tests that can monitor them during treatment. The initial testing will include 3,000 patients who have already completed their treatment and 3,000 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.
Samra Turajlic, project lead, Clinical Group Leader at the Francis Crick Institute, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, and Associate Honorary Faculty at The Institute of Cancer Research, London, said: “In the last ten years, we have made huge progress in the treatment of cancer with immunotherapy, but we are still underserving many patients due to treatment failure and side effects. We have a unique opportunity in the UK, given the NHS, to address this challenge.
“We are hugely excited to work together with such a large group of clinicians, patients and our industry partners, each with unique experiences and expertise. Research on this scale can get us one step closer to better tests in the clinic, but also fuel more discoveries regarding cancer immunology and new therapies. Ultimately, we want to speed up the delivery of personalised medicine for a disease that affects huge numbers of people across the UK every year.”
The project 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,
Also participating are six NHS Foundation 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
- The Christie NHS Foundation Trust.
MANIFEST will work with 11 industry partners:
- IMU Biosciences
- Oxford Nanopore Technologies
- Roche Pharma and Diagnostics divisions
- Roche imCORE network
- Molecule to Medicine
- Guardant Health
- Natera
- Microbiotica
- 10x Genomics
- Akoya Biosciences
- Univ8 Genomics.