A nationwide team of universities, hospitals and industry, led by the Crick and The Royal Marsden NHS Foundation Trust, have launched a new platform to understand immunotherapy response and side effects in cancer. Watch more via youtube here.

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.

Drugs that help the immune system fight cancer, collectively known as immunotherapy, are a frontline treatment for some types of cancer like melanoma (a form of skin cancer). 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.

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. 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 Crick, 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.

Zayd Tippu, Clinical Research Fellow at The Royal Marsden NHS Foundation Trust and the Crick, said:

By aligning the strengths of the NHS, academia, and industry, we aim to address some of the challenges faced in clinic, namely in improving outcomes for our patients. Profiling samples generously donated by over 6,000 patients will help redefine treatment approaches, drive discovery, and create opportunities to train the next generation of cancer researchers.

Jonathan Lim, project co-lead, Clinical Senior Lecturer at the University of Manchester, and Consultant in Advanced Immunotherapy and Cell Therapy at the Christie NHS Foundation Trust, said:

To tackle the biggest and hardest questions in oncology, we need real collaborative efforts. We are very pleased that this funding will enable us to join forces with the best across the UK to find innovative solutions to ultimately provide the best care for our patients with cancer.

Caroline Dive, Director of the Cancer Research UK National Biomarker Centre, said:

The CRUK National Biomarker Centre and Manchester Institute are proud to be part of this exciting MANIFEST consortium, that will discover and develop new biomarkers to optimise the use of the immunotherapies that are revolutionising cancer treatment.

Alex's story

Alex Green, 42, from Surrey, was initially diagnosed with Melanoma in 2012 and was treated with surgery.  Unfortunately, 3 years later the disease had managed to spread to his lymph nodes and Alex was referred to The Royal Marsden. Alex underwent several operations to remove the tumours, followed by a course of post-surgery radiotherapy, and later, immunotherapy.

Alex said: 

I finished radiotherapy and my scans were clear, however under two years later my cancer returned. I was offered immunotherapy and it completely saved my life. Without it, I was expected to have died in 2019, leaving behind my wife and two children, then aged four and seven.

It was a life-changing treatment for me and I’m now in my eighth year of complete remission and able to lead a normal and active life. Whilst the treatment’s results have been amazing, it did come with some tough challenges. I suffered from some pretty significant side effects, which resulted in me being hospitalised for two weeks. I’m very clear on the importance of researching and understanding immunotherapy side effects to make the treatment as effective and as kind as possible.

Department of Science, Innovation and Technology

MANIFEST launches as part of a commitment from the Department of Science, Innovation and Technology for funding to support cancer diagnosis and treatment.

Science and Technology Secretary Peter Kyle said:

Cancer is a disease that has brought pain, misery and heartbreak to every family in the country, including my own. But through Government working in partnership with the NHS, researchers, and business, we can harness science and innovation to bring the detection and treatment of this horrendous disease firmly in to the 21st century, keeping more families together for longer.

The UK’s scientists, researchers and captains of industry have brilliant ideas that aren’t just going to boost our health – they’ll boost our economy too, helping to build a virtuous circle for more investment in both health and research which will ultimately drive up living standards.

Working with industry

Industry partners in the consortium will bring expertise in novel technologies and immunotherapies, and will support the implementation of these discoveries in the clinic.  

UK-based company IMU Biosciences has joined the MANIFEST consortium to analyse thousands of blood samples from patients undergoing immunotherapy. They will use their detailed profiling platform to identify which immune cells are present in the bloodstream and use machine learning to predict whether individual variation in immune cells influences treatment response.

Adam Laing, President and CSO of IMU Biosciences, said: "The IMU team is thrilled to contribute our cutting-edge, AI-driven immune profiling platform to this groundbreaking UK consortium, helping to deepen the understanding of the immune system’s role in cancer therapy and response, with the ultimate goal of improving clinical outcomes for patients."

Collaborations

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, 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.

MANIFEST will work with 11 industry partners: IMU Biosciences; Oxford Nanopore Technologies; Roche Pharma and Diagnostics divisions, and the Roche imCORE network; Molecule to Medicine; Guardant Health; Natera; Microbiotica; 10x Genomics; Akoya Biosciences, and Univ8 Genomics.

The consortium will also collaborate with AstraZeneca; Bristol Myers Squibb; Immunocore; MSD; Amazon Web Services, and Indica Labs.

MANIFEST will also work with twelve networks across the UK to recruit patients to clinical trials and three patient organisations to make sure the research accurately represents the needs of people living with cancer (BRC RM/ICR Patient and Public Contributors Working Group; Melanoma Focus, and Action Kidney Cancer).