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Birmingham opens Europe’s first pancreatic cancer mRNA vaccine trial

Written by Louise Stanley on . Posted in Cancer outcomes, Clinical trials, Experimental medicine.

Researchers at BHP founding-members University Hospitals Birmingham NHS Foundation Trust (UHB) and the University of Birmingham have opened a trial to study how messenger RNA (mRNA) cancer vaccines may be used to prevent recurrence of pancreatic cancer. The Queen Elizabeth Hospital Birmingham (QEHB) is the first hospital in Europe to recruit into such a trial.

Pancreatic cancer is among the deadliest cancers globally, with a survival rate beyond 10 years of just 5% in England (2013-2017). It is often only when the cancer has reached an advanced stage that physical symptoms appear, at which point it becomes more difficult to treat.

The trial aims to recruit patients undergoing surgery to remove pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive disease that accounts for 90% of all pancreatic cancers.

Patients enrolled in the study will either receive an investigational cancer vaccine combined with chemotherapy (treatment group) or standard chemotherapy alone (control group).

In this investigational therapeutic cancer vaccine, mRNA is used to deliver the instructions for building several proteins (neoantigens) found in a person’s cancer. In doing so, the trial vaccine aims to train the immune system to recognise and attack the set of proteins (usually found on microscopic cancer cells) when it encounters it again.

Following surgery, samples of the patients’ tumour tissue and blood are sent to laboratories, to design and manufacture the investigational cancer vaccine. For the patients eligible for the trial, a mRNA-based cancer treatment is manufactured with mRNA specific to the proteins in that individual’s tumour.

This novel treatment approach is aimed at training the immune system to recognise and attack cancer cells, to potentially prevent cancer recurrence and increase the prospect of a patient being cured.

Dr Shivan Sivakumar, Principal Investigator of the trial, Associate Professor in Oncology at the University of Birmingham and Consultant Medical Oncologist at QEHB said: “We are incredibly proud that the Queen Elizabeth Hospital Birmingham is the first site in Europe to enrol a patient to this investigational pancreatic cancer vaccine trial. This achievement highlights Birmingham’s leading role in advancing cancer treatment, offering new hope for patients battling one of the most challenging cancers we face today.

“We recently also became the first site in Europe to open an immunotherapy study in cholangiocarcinoma (bile duct cancer), another deadly cancer. Birmingham is positioning itself to be a leading centre in Europe to test novel treatments for these hard-to-treat cancers and I find it humbling that patients in the Midlands have been able to enrol onto this trial, before anyone else in Europe.”

Professor Kiran Patel, Chief Medical Officer at UHB, which operates QEHB, added: “We are very fortunate to have exceptional infrastructure and world-class talent that positions us perfectly to lead in vital areas of cancer research.

“This trial showcases the expertise and dedication of our medical professionals, and the fantastic teams supporting them, who are at the leading edge of clinical research here in Birmingham.

“To be the first site to open in Europe, reaffirms our role as a national and international centre for cutting-edge oncology and highlights our commitment to improving patient outcomes through pioneering approaches.”

Jo Gray, Head of Research and Development Operations at UHB, said: “Through the National Institute for Health and Care Research (NIHR) Wellcome Trust Clinical Research Facility (CRF), we are able to provide expert care to patients receiving experimental therapies. Birmingham is the first site outside of North America to open and to enrol a patient onto this complex, early phase trial, that addresses an important need to identify better post-surgery treatments for pancreatic cancer.”

Professor Neil Hanley, Head of the College of Medical and Dental Sciences at the University of Birmingham, said: “This work epitomises why the University of Birmingham and its tremendous partnership with UHB is delivering life-changing impacts.

“Whilst such approaches were being investigated before 2020, we now know the power of mRNA vaccines from the COVID-19 pandemic; to tilt those discoveries from a time of tremendous challenge towards a much-needed world of new cancer treatments is inspiring for all of us.

“Birmingham is the ideal place to open this trial, with one of the leading pancreatic cancer units in the UK and serving a super diverse population. The chemistry between the university and hospitals is clear. By working as one team under the banner of Birmingham Health Partners, we are delivering the kind of cutting-edge research leading to transformational clinical care that befits Birmingham as an innovative city at the forefront of health and life sciences.”

Dr Chris Macdonald, Head of Research at Pancreatic Cancer UK, said: “For too long we have had so few treatment options for people with pancreatic cancer. Surgery is currently the only potential cure and yet, tragically, in 75% of cases the cancer reoccurs within a year. Finally, there is hope on the horizon.

“We are absolutely delighted that Queen Elizabeth Hospital Birmingham is the first site in Europe to enrol a patient to an individualised pancreatic cancer vaccine trial. We will be following the results with great interest, as the potential here cannot be understated. If this research proves successful, the vaccine could be a vital new weapon against the deadliest common cancer.”

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Researchers at the Royal Orthopaedic Hospital and Aston University explore novel bone cancer therapy

Written by Louise Stanley on . Posted in Cancer outcomes, Experimental medicine.

Lucas Souza, Research Laboratory Manager for the Dubrowsky Regenerative Medicine Laboratory at the Royal Orthopaedic Hospital (pictured), is partnered with Professor Richard Martin, director of the Advanced Materials Research Centre at Aston University to explore a new way to treat bone cancer.

As bone cancer researchers, we are seeking to tackle the problem of bone tumours across all fronts. We are currently exploring how the metal element gallium could be used to support the treatment of bone tumours due to its cancer-killing properties.

Bone tumours can be either primary (originated in the bone tissue) or secondary (originated in another tissue and metastasise to bone tissue). We have already proved in a previous study that primary bone cancer cells are four times more sensitive to gallium than normal cells. In that study we wanted to understand if doping bioactive glasses, used in orthopaedic and dental surgeries for its bone forming properties, with gallium would support positive outcomes for bone cancer patients. We were able to show that the use of gallium embedded in bioactive glasses is an excellent strategy to support bone repair whilst selectively killing bone cancer cells which can potentially culminate with better treatment outcomes and reduced cancer recurrence rates.

The next phase of this study is exploring the use of gallium against bone metastases – cancer that originated in another tissue before spreading to bone. The ultimate goal is to prove whether cells from bone metastases also have greater sensitivity to gallium so it could be used as an adjuvant medicine to control metastatic growth in the treatment of other types of cancer that usually metastasise to bone, such as breast, lung, and prostate cancer.

If successful, we will combine the gallium-doped bioactive glass powder with biodegradable polymers to make a minimally invasive injective gel that surgeons can use to treat both primary and secondary bone tumours. This gel will have the potential to reduce cancer recurrence and implant failure rates, leading to reduced time in hospital beds, reduced use of antibiotics, fewer revision surgeries, and increased survival rates.

It is also hoped that this innovation could be used to improve outcomes for patients with vertebral metastases and other types of primary bone tumours where surgery and radiation is less effective due to their proximity to the spinal cord.

The safety and effectiveness of these biomaterials will need to be tested further, but the initial results are really promising. Treatments for a bone cancer diagnosis remain very limited and there’s still much we don’t understand. Research like this is vital to support in the development of new drugs and new methodologies for treatment options.

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Behind the scenes – meet the ROH research team

Written by Louise Stanley on . Posted in Birmingham Health Partners, Clinical trials, Experimental medicine.

Written for BHP by Ellie Keeling, Lead Research Nurse at the Royal Orthopaedic Hospital

Birmingham is a major research hub with a thriving collaborative ecosystem convened by Birmingham Health Partners. Within this alliance, the Royal Orthopaedic Hospital (ROH) is leading the way in orthopaedic research, conducting clinical trials, observational studies, and laboratory research. Our work focuses on enhancing physiotherapy rehabilitation, developing therapies for bone tissue regeneration, and creating pharmaceutical treatments to reduce invasive surgeries and speed up recovery. ROH’s research aims to improve patient care, facilitate early diagnosis, support new drug development, and offer alternative treatments, consistently contributing new findings to the field.

The majority of this work happens behind the scenes. And the roles that make up this team are varied. They include our lab manager who oversees the management of the Dubrowsky Lab; research nurses; a research tissue bank co-ordinator; study co-ordinators; assistant clinical research practitioners; data managers; and a healthcare technician.

Research nurses play a vital role in delivering clinical research, guiding the patient as they go through the clinical research process and ultimately improving patient care and treatment pathways. It’s an incredibly diverse role, from recruiting patients for studies to collecting and tracking samples, and developing pathways to improve the delivery of trials. Because many clinical trials run over the course of several years, research nurses get to work with the same patients regularly and are able to build up a rapport with them.

Our research tissue bank co-ordinator manages our research tissue bank, which was established over thirty years ago and contains the world’s largest archive of frozen bone tumour samples – currently numbering 32,000 – including all orthopaedic malignancies as well as other benign and non-tumour tissue types. The research tissue bank is used by researchers across the globe who need access to bone and tissue samples that they can’t get elsewhere, with the samples supporting clinical projects to better understand cancers like chondrosarcomas (cancer of the cartilage cells) or develop new treatments for primary bone cancer.

The team is involved in a number of clinical trials, including the BASIS study and the RACER Hip and Knee studies. We are one of the main recruiting centres for the BASIS study, which is trying to find out which type of back brace is best for treating children and young people with scoliosis. The RACER Hip and Knee studies are exploring clinical effectiveness of robotic assisted hip and knee replacement. Pivotal to the success of these studies is patient recruitment – working closely with patients and recruiting them onto these clinical trials with empathy. Our assistant clinical research practitioners (ACRPs) are critical here, as this research couldn’t happen without the generosity of patient donations and their time. In this role, ACRPs work closely with patients to explain what research we are doing, explore how the patient could potentially participate in this research and support them through the process.

It’s essential that patient donations are viable and there are several steps required to ensure this. The role of the healthcare technician is a rare role, but a key one at ROH as it enables a clear and consistent pathway for the effective collection and packaging of patient bone and tissue samples.

Finally, our data managers keep all this work running smoothly by supporting the team with the collection and storing of patient data. This support helps our researchers identify what patient data could support new and existing clinical research as well as retrospective data-led research, all the while ensuring compliance and confidentiality.

While many research roles, especially in hospitals, are perceived as being behind the scenes, they are incredibly important bringing unique skills and knowledge and their contribution is crucial in making breakthroughs that can improve lives.

For more information on The Royal Orthopaedic Hospital’s research activities, visit Royal Orthopaedic Hospital – Research (roh.nhs.uk).

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World-first colorectal cancer vaccine trial treats first UK patient in Birmingham

Written by Louise Stanley on . Posted in Cancer outcomes, Clinical trials, Experimental medicine.

The Queen Elizabeth Hospital Birmingham (QEHB), operated by BHP founder-member University Hospitals Birmingham NHS Foundation Trust, has treated its first patient in England with a personalised vaccine against their bowel cancer, in a clinical trial which is part of NHS England’s new Cancer Vaccine Launch Pad (CVLP).

In a national first, father-of-four Elliot Pfebve received the developmental jab within the Clinical Research Facility at QEHB, one of several sites taking part in the colorectal cancer vaccine trial sponsored by BioNTech SE.

The trial is one of several that will be taking place in NHS trusts across the country to treat different types of cancer. Thousands more patients are expected to benefit from NHS England’s new CVLP, which will enable those wanting to participate in clinical trials to be fast-tracked to one of the nearest participating hospitals.

Patients who agree to take part have a sample of their cancer tissue and a blood test taken. If they meet a clinical trial’s eligibility criteria, they can be referred to their nearest participating NHS site, meaning patients from hospitals across the country will find it easier than ever to take part in groundbreaking research.

The investigational cancer vaccines evaluated in the colorectal cancer trial are based on mRNA – the same technology used for the Pfizer-BioNTech COVID-19 vaccine – and are created by analysing a patient’s tumour to identify mutations specific to their own cancer. Using this information, medics then create an experimental individualised cancer vaccine.

The developmental vaccines are designed to induce an immune response that may prevent cancer from returning after surgery on the primary tumour, by stimulating the patient’s immune system to specifically recognise and potentially destroy any remaining cancer cells.

The investigational cancer vaccines being jointly developed by biopharmaceutical companies BioNTech and Genentech, a member of the Roche Group, are still undergoing trials and have not yet been approved by regulators.

Higher-education lecturer Elliot, 55, had no cancer symptoms and was diagnosed through a routine health check with his GP.

A CT scan and a colonoscopy confirmed he had colon cancer and Eliott had surgery to remove the tumour and 30cm of his large intestine. He was then referred to the QEHB for initial rounds of chemotherapy and to take part in a clinical trial.

Eliott said: “Taking part in this trial tallies with my profession as a lecturer, and as a community-centred person. I want to impact other people’s lives positively and help them realise their potential.

“Through the potential of this trial, if it is successful, it may help thousands, if not millions of people, so they can have hope, and may not experience all I have gone through. I hope this will help other people.”

Thirty hospitals in England are already signed up to the pioneering Cancer Vaccine Launch Pad – one of the biggest projects of its kind in the world – with more sites joining the platform over the coming months.

The scheme aims to expand and work with a range of partners in the pharmaceutical industry to include patients across many cancer types who could potentially join a vaccine trial, such as those with pancreatic and lung cancer.

Principal Investigator for the trial at QEHB, Consultant Clinical Oncologist, Dr Victoria Kunene, said: “The investigational cancer vaccines are based on mRNA and are created by analysing a patient’s tumour to identify mutations specific to their own cancer. Using this information, we can create an individualised investigational cancer vaccine, but it is too early yet to say if these will be successful, though we are extremely hopeful.

“Based on the limited data we currently have of the in-body response to the vaccine, this could prove to be a significant and positive development for patients, but more data is yet needed and we continue to recruit suitable patients to the trial to establish this further.”

Amanda Pritchard, NHS chief executive, said: “Seeing Elliot receive his first treatment as part of the Cancer Vaccine Launch Pad is a landmark moment for patients and the health service as we seek to develop better and more effective ways to stop this disease. 

“Thanks to advances in care and treatment, cancer survival is at an all-time high in this country, but these vaccine trials could one day offer us a way of vaccinating people against their own cancer to help save more lives.

“The NHS is in a unique position to deliver this kind of world-leading research at size and scale, and as more of these trials get up and running at hospitals across the country, our national match-making service will ensure as many eligible patients as possible get the opportunity to access them.”

Trials have already enlisted dozens of patients, although the majority of participants are expected to be enrolled from 2026 onwards.

Professor Peter Johnson, NHS national clinical director for cancer at the NHS said: “We know that even after a successful operation, cancers can sometimes return because a few cancer cells are left in the body, but using a vaccine to target those remaining cells may be a way to stop this happening.

“Access to clinical trials could provide another option for patients and their families, and I’m delighted that through our national launch pad we will be widening the opportunities to be part of these trials for many more people, with thousands of patients expected to be recruited in the next year.”

Executive Director of Research and Innovation at Cancer Research UK, Iain Foulkes, said: “It’s incredibly exciting that patients in England are beginning to access personalised cancer vaccines for bowel cancer.

“This technology pioneers the use of mRNA-based vaccines to sensitise people’s immune system and in turn detect and target cancer at its earliest stages. Clinical trials like this are vital in helping more people live longer, better lives, free from the fear of cancer. If successful, the vaccine will be a game changer in preventing the onset or return of bowel cancer.”

Last year, the Government signed an agreement with BioNTech to provide up to 10,000 patients with precision cancer immunotherapies by 2030.

BioNTech has already begun conducting clinical trials in the UK, and the NHS launch pad is helping to accelerate the identification of eligible patients for those trials in England.

The vaccines being tested as part of the trials aim to help patients with different types of cancer and, if successfully developed, researched and approved, cancer vaccines could become part of standard care.

The NHS is working in partnership with Genomics England on the launch pad, with work already helping patients access the latest testing technologies and ensures they are given more targeted precision treatments for their cancer.

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New stromal cell treatment trial for chronic inflammatory diseases

Written by Louise Stanley on . Posted in Clinical trials, Experimental medicine, Inflammation and chronic disease.

People with chronic inflammatory diseases are taking part in a new cell therapy clinical trial that one participant said made them feel “miles better”.

The POLARISE trial, being organised by BHP founder-member the University of Birmingham and funded by a grant from Innovate UK is testing a type of cell therapy – stromal cells – to see whether they can resolve symptoms and inflammation in patients with certain autoimmune diseases including rheumatoid arthritis and primary sclerosing cholangitis.

A Phase 2 trial, POLARISE will investigate the safety and activity of ORBCEL – a stromal cell therapy that has been developed by Orbsen Therapeutics Ltd. Stromal cells are rare cells found naturally in the human body where they stimulate resolution of injury and inflammation via a natural healing process called efferocytosis. Stromal cells are also allogeneic – which means they can be purified from one donor and given to multiple patients without causing allergic reactions – so there is no need for donor matching.

These rare stromal cells are ethically sourced and purified from human donor tissue and expanded to therapeutic doses at the University of Birmingham’s Medicines Manufacturing Facility (MMF).

The ORBCEL therapy is administered intravenously across two visits with subsequent hospital appointments to check on the progress of their condition during a two-year trial period.

Philip Newsome, Professor of Hepatology and Honorary Consultant Hepatologist at the University of Birmingham is leading the POLARISE trial, and explained: “Stromal cells are an exciting potential treatment for inflammatory diseases. These diseases are debilitating and very hard to treat as the body has switched a natural defence system for dealing with threats to one that starts attacking itself. It’s therefore critical to find ways to support the body to naturally deal with inflammation rather than turn off the defences which can lead to all sorts of infections. Early results from previous trials using Orbsen’s ORBCEL stromal cell therapy are encouraging and we’re hopeful that the treatment will be beneficial for some patients.”

Stromal cells such as Orbsen’s ORBCEL therapy can be purified from bone marrow or umbilical cord tissues donated by healthy individuals with donor consent under ethical approval by the Anthony Nolan Trust. While each single bone marrow or umbilical cord contains only few thousand stromal cells – these cells can be purified by Orbsen’s technology to undergo controlled expansion in cleanroom bio-reactors to produce a thousand allogenic doses of ORBCEL from each tissue.

Within the Innovate UK-funded Advanced Therapies Treatment Centre (ATTC) Consortium and POLARISE trial – these tissues are transported from the Anthony Nolan centres to the Advanced Therapies Facility (ATF) at the University of Birmingham – where Orbsen and ATF staff collaborated to purify and manufacture doses of Orbsen’s Stromal cell therapy – ORBCEL- using patented technologies and Terumo’s Quantum Cell Expansion Bioreactors.

Orbsen Therapeutics Chief Scientific Officer, Steve Elliman said: “We are delighted to continue our significant and productive clinical collaborations with Prof. Newsome, the University of Birmingham – and the Anthony Nolan Trust – to determine the safety and efficacy of our ORBCEL therapies in patients with chronic inflammatory diseases.

“These First in Human (FIH) trials are difficult to undertake and deliver – even more so during the COVID19 pandemic. These trials are not possible without brave patients – like Hannah Dines – who volunteer to participate in these rigorous safety trials. And so, we take this opportunity to thank the patients, nurses and clinical teams who work so hard to complete these invaluable studies.

“We look forward to completing these important safety trials and look forward to examine how ORBCEL can encourage resolution of symptoms in patients with chronic inflammatory disease.”

The Innovate UK-funded POLARISE trial represent the third major clinical trial collaboration between The University of Birmingham and Orbsen Therapeutics to assess the safety and efficacy of Orbsen’s ORBCEL therapy. Professor Phil Newsome is also leading the EU FP7 funded MERLIN clinical trial that is assessing ORBCEL as a therapy for patients with autoimmune liver diseases. The MERLIN trial is complete and is expected to report in the first half of 2024.

Orbsen is also collaborating with Prof Paul Cockwell at the University of Birmingham and Professor Giuseppe Remuzzi at the Mario Negri to assess the safety of ORBCEL as a therapy for Chronic Kidney Disease caused by Type 2 diabetes, in a Phase 1/2 clinical trial called NEPHSTROM. Professors Cockwell and Remuzzi recently published the first results from NEPHSTROM in the prestigious Journal of the American Society of Nephrology (JASN). In the NEPHSTROM trial publication in JASN, a low dose of ORBCEL was reported to be safe and promote stabilization of kidney function over 18 months in patients suffering with Progressive Chronic Kidney Disease and type 2 diabetes.

Patient story – Hannah Dines, Rio 2016 Paralympian

Self-confessed ‘type A person’, Hannah Dines is one for setting mad goals. Born with cerebral palsy, freelance writer and sportswoman Hannah trained and raced for Great Britain in para-cycling including racing at the Rio 2016 Paralympic games, and now represents GB in adaptive surfing.

However, in 2021 during the buildup to the delayed Tokyo games Hannah was diagnosed with a chronic inflammatory disease called Primary Sclerosing Cholangitis (PSC) in which the bile ducts in the liver get progressively narrower can lead to liver failure and impacts other organs like the spleen, intestines and bowel.

Hannah explains: “I was diagnosed with PSC after struggling with major fatigue and worsening of my spasticity from my cerebral palsy. I would train and feel very ill but do it anyway. I love moving my body and during the training I still felt that joy. Still, I began to fear the symptoms that would come after. I used to call it having an ‘exercise hangover’ though I rarely drank alcohol and was in my twenties. I would ensure I had at least four hours after training to collapse in bed, too tired to even watch TV, feeling too ill to sleep, known as malaise.”

“By the point of diagnosis though I was really ill and sleepy every day, I couldn’t focus but I kept pushing with my training, a part time job and then bed. Finally, a clinical doctor took my blood to put me on an alternative spasticity medication that required a liver function test. That’s when I was sent to a liver clinic and they took a liver biopsy right away and found out my sclerosis was pretty serious.

“It made all my symptoms make sense and because I was young and sporty no-one misdiagnosed me with fatty liver or alcoholism, which was nice, even if it didn’t really lessen the impact of having PSC.”

After receiving her diagnosis, qualified physiologist Hannah knew she wanted to try and take part in a clinical trial although received a series of rejections due to the advanced nature of her PSC.

Hannah continues: “I was recommended for POLARISE and I didn’t hesitate. The day after my first dose I felt incredible and not just because the clinicians administering the drugs were so nice. This effect lasted a couple of days and I truly felt released from PSC.”

“I was still competing at a sport: adaptive surfing and I booked all my contests because I knew I wouldn’t need to cancel. I laughed out loud on an aeroplane because I felt real energy for the first time in years. It was probably the steroids or a placebo effect but my liver function tests also got much better.

“My second dose was a little underwhelming compared to my first, but I still felt miles better. My “malaise” and feeling kind of “dead” had gone away.

“I used to obsess over my blood values and stopped checking them. I started setting goals more than two months in advance, which I had decided not to do after a year of having to cancel everything. We’re now six months and I still big hits of malaise but just to know that respite might be possible like at the start of my trial…that’s really special..

“All I can do is hope the findings are positive and this can become a regular treatment for people with PSC. No matter the result of POLARISE it has given me real hope for the future.”

Not letting PSC stop her, Hannah has taken up adaptive surfing and last year represented GB at the world championships, finishing fourth in her category and supporting Team GB to their most successful championships yet.

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Treatment hope for patients with rare disorder following clinical trial

Written by Louise Stanley on . Posted in Clinical trials, Experimental medicine.

Patients with a rare hereditary disorder may soon benefit from a new treatment which has undergone a promising trial at Queen Elizabeth Hospital Birmingham (QEHB) – part of BHP founder-members University Hospitals Birmingham NHS Foundation Trust.

The experimental drug, called mRNA-3927, has been tested on patients for the first time as part of a study into propionic acidaemia – a serious metabolic disorder which means the body is unable to process certain parts of proteins and fats properly. This can lead to a build-up of harmful substances in the body and, without appropriate treatment, can be fatal.

Patients with this condition must follow a specific diet, including a low protein intake and specific food for life. Symptoms include: vomiting, lethargy, dehydration, and acid build up in the body. Liver and kidney transplant is a surgical option that can help reduce the frequency of acute metabolic episodes.

QEHB is the only adult centre in the world running this study whose initial findings have just been published.

Prof. Tarekegn Hiwot, Consultant in Inherited Metabolic Disorders at QEHB and Honorary Professor in the Institute of Metabolism and Systems Research at fellow BHP founder the University of Birmingham, led the trial and recruited patients for the study. He said: “We conducted a study of mRNA-3927 with 16 participants to find the safety, tolerability, and optimal dose. Our interim analysis has shown significant reduction of 70% in preventing severe metabolic crisis. The treatment was safe and well tolerated.

“In summary, this study explores a promising, first of its kind treatment for propionic acidaemia using mRNA-3927, aiming to improve patients’ health and reduce dangerous metabolic events.

“This study may also serve as a proof of concept in using mRNA treatment for other life limiting single gene genetic conditions in general.”

The interim results of the study were published in Nature.

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