A patient at Clatterbridge is the first person in the world to be given a pioneering cancer vaccine for the most common type of lung cancer.
Clinicians and researchers at The Clatterbridge Cancer Centre (CCC) and the University of Liverpool, including the Liverpool Clinical Trials Centre (LCTC), are studying the bespoke vaccine, designed to match the unique genetic changes found in patient Chris Jones’s tumour in this early-stage clinical trial.
Chris, who lives in Hoylake, on the Wirral, has advanced lung cancer that has only partially responded to standard immunotherapy treatment and it is hoped the vaccine will ‘boost’ her immune system to recognise tumour cells and attack them after searching them out in her body, so that she can benefit from her cancer treatment for longer.
Advanced computational technologies, developed by biopharmaceutical company myNEO, identify which tumour-targets the immune system should be aimed against to strengthen the anti-tumour immune response. These targets are manufactured into a vaccine with the use an innovative cell-free manufacturing method to make DNA known as ‘doggybone DNA’ (dbDNATM). This technology allows researchers to produce personalised vaccine components rapidly and at a lower cost than more traditional methods.
dbDNA is part of the portfolio of proprietary DNA manufacturing solutions provided by UK-based Touchlight, the market leading synthetic DNA provider, which uses enzymes to amplify DNA efficiently in a laboratory setting, simplifying production.
The CCC researchers believe the inclusion of the dbDNA technology will, in future, play an important role in making personalised cancer vaccines capable of delivery at scale, with the collaboration between Clatterbridge and Touchlight providing an important clinical opportunity to demonstrate these benefits.
The trial will involve 10 participants with advanced non-small cell lung cancer. Its main aims are to assess safety and to look for early signs that the personalised vaccine might trigger an immune response against this common cancer. In the UK, around 50,000 people are diagnosed with this type of cancer each year, with two million cases globally, making it the third most prevalent cancer in the world.
Chris was referred for tests last year by her GP following a persistent cough and breathlessness. Her father and grandfather died from lung cancer and her worst health concerns were confirmed when she, too, was diagnosed with the disease.
Chris was given immunotherapy but it was not tackling the disease, and she was offered the opportunity to join the NEOVACC clinical trial.
Chris runs gelato and coffee shop Churn & Chill, in Hoylake, with her daughter, Phoebe – and has been working throughout her treatment – while her other daughter, Grace, is a firefighter. Chris’s first daughter, Alex, died in 2016 from breast cancer aged just 26, three years after her diagnosis.
Alex spent those years raising money for cancer charities and working with the CoppaFeel! educational organisation, raising awareness of self-checking to aid early diagnosis of cancer.
Chris, 68, said: “Alex raised a lot of money for cancer research, so I knew how important research was in the battle against cancer.”
“The trials team said I was an ideal candidate for this study, so I didn’t hesitate when they asked if I wanted to take part. If there was a possibility of me surviving longer, I was happy to be involved with it, and if there is a chance of it helping other people in the future, then that was even better.
“This type of research is very new but could add a new range of treatments to what patients are given already – and it could also give me a chance.
“Perhaps in the future patients with the type of breast cancer that Alex had could benefit from this new therapy. Alex was unable to join a clinical trial, so if this research could help someone in her position in the future, then that would be really positive.”
The NEOVACC Phase I trial brings together experts from many different disciplines, including cancer doctors, immunologists, genetic scientists, clinical trial specialists, NHS teams and industry partners, underpinned by a £2.66m grant from the Medical Research Council’s Development Pathway Funding Scheme.
Chris was given her first round of the cancer vaccine at Clatterbridge Cancer Centre, Liverpool, using the Pharmajet’s Stratis system, a needle-free injection that enhances DNA cancer vaccine performance through optimised delivery to the muscle. She will receive further doses of it over several months alongside standard immunotherapy treatment.
The study is led by Professor Christian Ottensmeier, CCC Consultant Oncologist, and Professor Natalia Savelyeva, who are both part of the University of Liverpool’s Institute of Systems, Molecular and Integrative Biology.
Chief Investigator Prof Ottensmeier said: “This personalised approach could offer hope to those for whom standard immunotherapy has not fully worked, by helping the immune system recognise and fight the parts of the tumour that have previously evaded detection. I hope this research will contribute to new ways of thinking about cancer vaccine use in advanced lung cancer.
“We are excited to be using ‘doggybone’ technology in the creation of this vaccine, which has the potential to be a gamechanger in reducing the speed and cost of production of these important therapies.”
Professor Savelyeva said: “It is a very exciting study because, if successful, this strategy could benefit more than half of patients with advanced lung cancer, and possibly those with other types of cancer as well. Cancer vaccines hold the promise to turn ‘immune cold’ cancers into ‘immune hot’ cancers and if successful could help more than 50% of patients with advanced lung cancer and potentially also patients with other cancers. We are very excited to develop this trial and look forward to making the vaccines available to the patients with non-small cell lung cancer that are seen in our region.”
Dr Carles Escriu, CCC Medical Oncology Consultant and University of Liverpool Senior Clinical Lecturer, who is leading on the clinical aspect of the study, said: “While a minority of patients experience long‑term benefit from immunotherapy, most either do not respond or eventually develop resistance. This study is unique internationally – not only because of the novel technology, but because it focuses on a substantial and clinically important group: patients who respond initially but are at high risk of developing resistance. Cancer vaccines are typically well tolerated, which is particularly relevant for lung cancer patients who are often frail and have significant comorbidities. A less toxic treatment capable of extending survival would be highly valuable in routine clinical practice.”
The NEOVACC clinical trial is being conducted in the Liverpool Clinical Research Facility at The Clatterbridge Cancer Centre. It is supported by a wide-ranging partnership that includes The University of Liverpool, including the Liverpool Clinical Trials Centre and the GCP Laboratory team, and The Clatterbridge Cancer Centre, which are collaborating closely with Touchlight Genetics Ltd, NHS Blood and Transplant, GenomeScan, myNEO Therapeutics and PharmaJet, with funding from the Medical Research Council through the Development Pathway Funding Scheme.
Sophie Mountcastle, Translation Programme Manager at Medical Research Council, said: “The first UK patient receiving this personalised cancer treatment is a great example of what public investment through the MRC can achieve. This pioneering clinical trial is developing a therapeutic vaccine designed to stimulate the immune system to recognise and attack tumour cells based on the tumour-specific genetic changes that make each patient's cancer unique, offering a potential new approach for patients who do not fully benefit from existing immunotherapies. By bringing together researchers, NHS clinicians, and industry partners, we’re helping to translate scientific discoveries into potential new treatments for patients, while advancing the next generation of personalised cancer treatments.”
Dr Jill Makin, Chief Scientific Officer, Touchlight Genetics Ltd commented: “We are very excited to work with Profs Ottensmeier and Savelyeva. The doggybone DNA technology provides an ideal means to deliver rapid individual personalised vaccines to this large group of patients with an unmet clinical need and other patients with solid cancers.”
Paul Lloyd-Evans, Head of the NHS Blood and Transplant Clinical Biotechnology Centre manager, said: “We will do the final work turning the drug into vials of medicine. We have the specialist MHRA licences, GMP-grade clean rooms, and UK-leading expertise, to ensure groundbreaking cell and gene therapies reach patients to the highest standards. Our NHSBT Liverpool Therapeutic Apheresis Services team is also a critical part of this trial. Before and after the patient is given the vaccine, the TAS team will use specialist machines to separate out some of Chris’ blood cells. These cells are tested before and after treatment, to evaluate the effectiveness of the vaccine.”
Stefanie Klaver-Flores, Head of Oncology at GenomeScan GenomeScan added: “The NEOVACC trial represents an important step forward in the development of truly personalised cancer immunotherapies. We are excited to work alongside the NEOVACC team and our partners on this pioneering study. By combining genomic sequencing with bioinformatics, we can help identify the unique tumour-specific mutations that form the basis of these personalised vaccines. We are proud to contribute our expertise in genomic profiling and support research that has the potential to expand treatment opportunities for patients with advanced lung cancer. This collaboration demonstrates the importance of bringing together clinical, academic and industry expertise to advance innovation in precision oncology.”
A spokesperson for myNEO Therapeutics said: “Every one of these vaccines is built around the specific mutations that make a patient's tumour unique. At myNEO, that is exactly what our ImmunoEngine platform is designed to find: pinpointing the targets on each individual tumour that the immune system has the best chance of recognising.”
Wouter Latour, President and CEO, PharmaJet, Inc. commented: “The future of cancer treatment will depend on bringing together breakthroughs in genomics, vaccine design, manufacturing and delivery. We are excited to contribute PharmaJet's needle-free technology to the NEOVACC collaboration and help advance a personalized immunotherapy approach that could ultimately benefit patients with lung cancer and many other solid tumours.”
Prof Ottensmeier added: “This is the first personalised cancer vaccine trial spearheaded by academic research, using our own vaccine concepts. It has been a monumental task to achieve the green light for this research, and I would like to thank our many partners and everyone who has contributed to us getting this far.”
