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3d rendering of red blood cells in vein

New research collaboration will develop precision cell therapies for blood disorders

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

The Universities of Birmingham and Oxford are to take part in one of five NHS Blood and Transplant (NHSBT) research units launched today.

The £20m programme, co-funded by the National Institute for Health and Care Research (NIHR) and NHSBT – is aimed at providing new technologies, techniques or insights that will benefit donation, transfusion, and transplantation. The NIHR BTRUs are partnerships between universities and NHSBT.

Many of the work strands in the new units could result in new technologies and practices that can then be delivered at scale by NHSBT, helping to save and improve even more lives. Much of the work will be aimed at reducing health disparities and improving access to new treatments.

Researchers at the Universities of Birmingham (UoB) and Oxford are part of the NIHR BTRU in Precision Cellular Therapeutics – also working in collaboration with University Hospitals Birmingham (UHB) NHS Foundation Trust. UoB and UHB are both founding members of BHP, with a long history of collaborative research and development.  

The aim is to develop new kinds of cell therapies for blood disorders and blood cancer, and improved systems for following up patients receiving treatment to better support their care.

There is a wide range of work in the package but examples include:

    • Transplants work in blood cancer patients because some of the donor immune cells attack and eliminate the cancer, but these cells can also attack the donors own cells and cause a complication called graft versus host disease (GvHD).  The team will seek to identify and clone the receptors that enable the T cells to target the cancer cells while reducing the toxicity due to GvHD seen in patients. The ultimate aim of this research is develop a novel clinical trial, with NHSBT, via its cell therapy manufacturing infrastructure, expanding these cancer specific T cell receptors for use in patients.
    • There is a shortage of suitable cell donors for minority communities.  Cord blood units from babies may be a match but not have enough cells to be successful in adults. The team will seek to expand and gene edit the stem cells in cord blood, so they could be used with increased safely in a wider range of adults.  NHSBT will support the translation of this research through to early phase clinical trials, providing process development, manufacturing and quality control expertise.  This initiative will drive wider access to cord blood transplant.
    • It is important that patients from all communities benefit from cell therapies.  The team will seek to better understand how patients access the newer cell therapies and how they perceive the benefits of treatment.  The team will develop new digital technologies that improve care by enhancing interactions between the patients and their doctors and nurses.

The BRTUs are funded by £16m from the NIHR and £4m from NHSBT, with research goals set to meet NHSBT’s requirements, to be delivered between 2022 and 2027.

The products could be manufactured at the latest NHSBT sites including major new centres such as the new cellular therapies laboratories in Barnsley and the forthcoming Clinical Biotechnology Centre in Bristol.

Dr Gail Miflin, Chief Medical Officer for NHSBT, said: “By collaborating with academia, these five new Blood and Transplant Research Units will help us to deliver on our mission to ‘save and improve even more lives’ and drive innovation to inform future clinical practice and improve patient outcomes.

“For example, the supply-demand gap for solid organs continues to grow. We will explore the use of organ perfusion technologies to maintain and enhance the quality of organs, improve organ preservation and increase organ utilisation. This will enable more patients to receive the transplant they need.

“And by building and analysing new data sets to track and demonstrate the impact of our interventions will lead to better understanding and improved outcomes. We already do this well for solid organs, but do not currently understand the outcomes for people who receive blood or stem cells. We will work with partners to build integrated data sets for these patients, focusing on the multi-transfused, especially those with sickle cell disease where a clear health inequity exists.

“To maximise the value and impact from our research, we will accelerate the translation of innovation into practice. The NIHR BTRUs will be an important vehicle for this in the longer term.”

Experts at Birmingham Women’s and Children’s develop new test to spot rare eye cancer in unborn babies

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection.

Experts from BHP members Birmingham Women’s and Children’s Hospitals have developed a life-saving test that allows doctors to spot a rare form of eye cancer in babies in the womb.

The test, which is being rolled out by the NHS in England this week, means that babies identified as being at risk of developing retinoblastoma can be monitored and treated sooner – increasing the chance of saving their eyesight and potentially their lives.

Symptoms of retinoblastoma are hard to detect and a diagnosis can normally only be made once the tumour has progressed and the eye can’t be saved.

The new non-invasive test can detect changes in the genes in DNA and is likely to identify around 50 infants with retinoblastoma each year, in the latest example of the NHS harnessing the power of genomics to diagnose and treat patients faster and more effectively.

Non-Invasive Prenatal Diagnosis (NIPD) also means parents can be informed early in pregnancy if their child is at risk.

The blood sample test is taken from the mother before birth and tested and analysed for mutations, which can determine with almost 100% accuracy if the baby will develop retinoblastoma.

Treatment can then start on the affected eye as soon as the baby is born, with doctors closely monitoring the other eye for any signs. The test can also predict if the disease might develop in their siblings and will be offered to families where there is a confirmed case of retinoblastoma in the family.

In addition to the cutting-edge new test, Drs Trevor Cole and Amy Gerrish, who have been part of our specialist retinoblastoma service, are also developing a non-invasive post-natal cancer test for retinoblastoma patients using eye fluid – which can also identify if a patient is at risk from other cancers later in life. It’s hoped that in the future, this could be eventually done by a simple blood test.

Dr Amy Gerrish said: “The introduction of this technology of cell free DNA analysis will revolutionise the management of all aspects of retinoblastoma from early detection, selection of the best treatments, identification of family members at risk of retinoblastoma and early detection and treatment of associated adult onset cancers.

“We also believe it will help address the huge discrepancy in retinoblastoma outcome for individuals in high income and low and middle income countries which has been highlighted by the World Health Organisation (WHO)”.

NHS Chief Executive Amanda Pritchard said: “The introduction of this pioneering new test is fantastic news for babies and their parents and has the potential to save hundreds of lives over the coming years.

“Cancer is such a terrible illness and a baby being born with it can have a huge impact on parents and families during what should be an incredibly happy time, but backed by world-class innovation and services like the NHS Genomic Medicine Service, through the Long Term Plan the NHS is developing and delivering more cutting edge treatments like this one to help save lives and keep families together”.

Mum Siani Bainbridge, 22, from County Durham, had retinoblastoma herself as a child and feared her baby boy, Oscar, might carry a faulty gene known as RB1 which causes the potentially deadly cancer.

But she was relieved when she took part in a new trailblazing test, where doctors were able to spot the previously hard-to-detect disease and allay her concerns with a programme of treatment straight after his birth.

Siani said: “This took away a lot of stress, knowing that if there was going to be anything wrong then he would be helped straight away.

“Given that the tumours were quite severe when he was born, the fact he could be treated straight away definitely affected his outcome. It was nice to know the day he was diagnosed it was ready, set go”.

Just a week after being born, Oscar started his cancer treatment, which involved chemotherapy and then laser therapy.

While doctors could not save the sight in one eye, they did avoid having his eyeball removed and crucially, he kept his perfect sight in the other eye – as well as avoiding the disease potentially spreading to the brain.

Consultant Clinical Scientist Stephanie Allen, at Birmingham Women’s Hospital, said: “An early diagnosis will allow clinicians to manage, monitor and prepare treatments much earlier which can transform the prognosis for the baby.

“It will also give the family certainty and allow them to prepare for the birth knowing the support the clinical team will give them”.

The NIPD is one of more than 15 new tests and amendments being added to the National Genomic Test Directory (NGTD), which outlines the genomic tests available via the NHS in England through the NHS Genomic Medicine Service (GMS).

The directory, which is the only one of its kind, covers more than 3000 rare diseases and over 200 types of cancer – demonstrating how the NHS is a world leader in harnessing the benefits of genomics, the study of the genes in our DNA and their function, to deliver better patient care.

Among the other additions to the directory are tests for gene mutations that cause forms of breast and endometrial cancer, acute myeloid leukaemia and several rare diseases. A genetic test for a particular type of advanced lung cancer has had a matching treatment recently approved by The National Institute for Health and Care Excellence (NICE), meaning more effective treatment for patients.

Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in NHS England said: “This new test is a perfect example of how the NHS Genomic Medicine Service is harnessing cutting-edge technology to deliver genomic tests for cancers like this and many other conditions through the National Genomic Test Directory – meaning more comprehensive and earlier diagnoses and more targeted treatments sooner for all our patients”.

Patrick Tonks, Chief Executive of The Childhood Eye Cancer Trust (CHECT): “Any developments such as this new diagnostic test which has the potential to allow treatment to be started much sooner and therefore the real potential to improve patient outcomes is very exciting news for babies and for the families of anyone affected by retinoblastoma. We watch with interest as this new development is rolled out across the country”.

Health and Social Care Secretary Sajid Javid said: “Despite the unprecedented pressure put on the NHS because of the pandemic it is incredible to see continued life-saving innovation taking place, enhancing cancer care and diagnosis even before birth.

“Early diagnosis is vital to ensure these babies are given every opportunity to see, and the best chance of survival. New tests such as these will help clear the COVID backlog, ensuring patients are seen at the right time and provided the right care.

“Our 10-Year Cancer Plan will set out how we will lead Europe in cancer care, improving outcomes for patients across England”.

Urine test for bladder cancer could replace thousands of invasive procedures each year

Written by Louise Stanley on . Posted in Cancer outcomes, Clinical trials, Early diagnosis and detection.

Birmingham researchers funded by Cancer Research UK and liquid biopsy company Nonacus have developed a new urine test for bladder cancer, which could reduce the need for invasive and time-consuming procedures to diagnose the disease.

The test will use highly sensitive liquid biopsy technology developed by Nonacus in conjunction with  a panel of biomarkers developed and validated by Mr Rik Bryan and Dr Douglas Ward from the Bladder Cancer Research Centre at BHP founder-member the University of Birmingham, to detect the presence of bladder cancer by finding DNA from tumour cells present in the urine.

The biomarker panel, which consists of 443 genetic mutations that are common in bladder cancer has been validated in a deep sequencing study recently published in European Urology Oncology.

In this study, which was funded by Cancer Research UK and the Medical Research Council, the researchers used the test to analyse urine from 165 people with bladder cancer that had experienced haematuria (blood in the urine), and successfully detected the disease in 144 of them (87%).

The researchers also looked at using the test in 293 patients who had already been treated for bladder cancer and were being monitored for the cancer returning. In this setting, the test returned a higher proportion of false positive results compared to when used in the haematuria clinic (37.5% vs 15.2%), with 99 positive urine tests without a tumour being seen by cystoscopy on the same day. However, during their follow up monitoring, the patients who had those positive results had almost 3-times higher (11% vs 4%) rates of the cancer returning within 24 months indicating that the test could help detect recurrent disease before it is visible by cystoscopy (the camera inspection of the bladder). Further research is needed for the test to be used for surveillance.

Lead researcher Mr Richard Bryan said: “Even though cystoscopy is good at detecting bladder cancer, it’s invasive and time consuming for patients, so we need a better way to diagnose patients. In the future our test could be an easier way to get people with bladder cancer diagnosed faster, and could mean that tens of thousands of cystoscopies on healthy patients can be avoided each year.”

Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK said “These findings show that this urine test could help diagnose bladder cancer more easily. Early detection of cancer is key for improving patient outcomes and research like this could help identify the patients that need treatment soonest, while easing the pressures of diagnostic procedures on the NHS. We look forward to seeing how the test performs in the next clinical trial.”

The researchers are working in partnership with Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, to turn their approach into a clinical test for patients to be used within the NHS, and will start a clinical study funded by Cancer Research UK and involving over 3000 patients to evaluate just how powerful the test is at reducing the number of cystoscopies.

Each year, over 300,000 cystoscopies are carried out in England, however, around 80% of patients with haematuria who’ve had cystoscopy are found to have no cancers or abnormalities1,2.  The researchers believe that using the urine test in haematuria clinic could reduce the number of patients requiring a cystoscopy by at least 45%.

Funding boost to help improve ovarian cancer survival rates

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection, Health inequalities.

BHP’s newest member NHS Trust has been given a charity grant of £100,000 to help improve survival rates of women with ovarian cancer.

The Pan-Birmingham Gynaecological Cancer Centre, based at SWBH’s City Hospital, is working jointly with University of Cambridge to boost the uptake in genetic testing, especially in Black, Asian and Minority Ethnic communities (BAME) where survival rates are low.

The project, called the Demonstration of Improvement for Molecular Ovarian cancer testing (DEMO), will create information about genetic testing in various languages both in leaflet and video format. The project will also improve the quality of the sample taken to aid diagnosis when there is suspicion of ovarian cancer by establishing a guidance document for all healthcare professionals involved in the process.

Dr Elaine Leung, Clinical Lecturer and Specialist Registrar at the Pan-Birmingham Gynaecological Centre which is run by Sandwell and West Birmingham NHS Trust, said: “This is a much-needed project reaching those diverse communities in the area.

“With the support of our patient representatives, the materials we co-create will be in an easy-to-understand format in both written and video form, which will give women a better understanding of the link between cancer and genetic testing.

“It’s important to ensure women know that genetic testing is similar to early detection and can help prolong life – we have already seen evidence of this through other studies.

“It helps to provide tailored treatments for patients and ultimately can mean surviving an ovarian cancer diagnosis.

“The lack of informed decision-making resources for women whose first language is not English could be a contributor to the low rates of testing within these communities. The team will co-produce information in multiple languages, as well as exploring why some groups of women are more likely to decline genetic testing.”

The project has been funded by health charity Ovarian Cancer Action and is part of a wider national initiative which includes funding for five other NHS cancer centres.

The Pan-Birmingham Gynaecological Cancer Network delivers cancer care to more than two million people in the West Midlands.

The project also builds on the team’s previous experience with the genetic testing studies, looking at BRCA testing in women with a new diagnosis of ovarian cancer before it became mainstream practice.

Lisa Bird, a former cancer patient who is part of the project, said: “When I was in my thirties I was diagnosed with ovarian cancer, which was a large shock.  My first line treatment successfully got me into remission but I wanted to know what options would be available to me if I came out of remission.

“I investigated treatment options and found that there were some treatments only available to those that have the BRCA 1 and 2 genes.  I also wanted to know if other family members were at an increased genetic risk of also getting ovarian cancer, so that I could warn them of the symptoms and ensure that they received better monitoring by their GPs.

“I’m really pleased to be part of the DEMO project team that will encourage more patients to have these same tests. I’m passionate that anyone affected by ovarian cancer should be able to have this genetic knowledge so that their healthcare teams can give them the best treatments available to them as quickly as possible. I really believe that the results of this project will help to provide patients with ovarian cancer, with a greater chance of an extended life.”

New blood cancer gene defect can be treated with existing drugs

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

A defective gene normally found in blood cancers could be treated with drugs already available for cancers with similar gene defects, scientists at BHP founder-member the University of Birmingham and Queen’s University Belfast have revealed.

The research team, funded mainly by Cancer Research UK and the Medical Research Council, found that tumours with mutations in the SF3B1 gene respond to PARP inhibitors – a type of drug used to treat cancers which have similar mutations in the BRCA1 and BRCA2 genes.

The researchers believe that PARP inhibitors could be used to treat patients with tumours carrying the defective SF3B1 gene. This mutation is most often found in blood cancers, including chronic lymphocytic leukaemia, as well as some rare cancers like uveal melanoma.

Co-author Professor Grant Stewart, of the University of Birmingham, said: “Our work demonstrates that a molecular understanding of how a specific gene mutation affects a cancer cell’s ability to repair damaged DNA can be exploited clinically to specifically tailor the anti-cancer therapy used to treat an individual’s tumour. This will increase the effectiveness of the therapy and hopefully, reduce the chances of re-occurrence.”

Dr Kienan Savage, lead author and Reader at Queen’s University Belfast, said: “Our findings have clinical implications for the treatment of many cancers. We specifically focused on this genetic mutation as it is found in several difficult to treat leukaemias and other cancers, and it affects so many cancer patients. By deepening our understanding of this gene mutation, we have identified new ways of treating these cancers that could improve survival rates.”

PARP inhibitors, which include olaparib and rucaparib, are used to treat some patients with ovarian, breast, prostate and pancreatic cancers – usually patients who have inherited a faulty BRCA1 or BRCA2 gene. Around 1 in 400 people have a faulty BRCA1 or BRCA2 gene.

The research – published in Cancer Research, a journal of the American Association for Cancer Research – found that the SF3B1 mutation produces similar effects to the faulty BRCA1 gene by damaging DNA, preventing it from being repaired properly, and stopping it from making normal copies of itself. PARP inhibitors target the cell’s DNA repair tools by locking them in place on the DNA. This stops DNA repair, causing the cancer cells to die.

The scientists found that cancer cells with the SF3B1 mutation were sensitive to olaparib, the most common PARP inhibitor, some specific chemotherapies and to radiotherapy. The scientists believe that the SF3B1 mutation disrupts the cell’s ability to make DNA repair proteins, leaving it vulnerable to drugs which target these proteins.

The SF3B1 mutation occurs in up to 30% of blood cancers called myelodysplastic syndromes, where blood cells don’t form properly. They are difficult to treat as they occur predominantly in older patients who may not be considered fit for treatment. The mutation is also common among uveal melanoma or cancers of the eye, which currently have limited treatment options.

Dr Katrina Lappin, of Queen’s Univesity Belfast and first author of the study, added: “Our research shows that cancers with these specific mutations, may be treated effectively with PARP inhibitor therapy drugs, which are less toxic, better at killing cancer cells with these mutations and can be taken at home in tablet form. This could have huge implications for improving outcomes and quality of life of people with these cancers. This work will pave the way for clinical trials using PARP inhibitors for the treatment of patients with this commonly associated cancer mutation, allowing a more personalised approach to the treatment of these cancers.”

The researchers now want to test PARP inhibitors in clinical trials with patients who have the SF3B1 mutation to see if they can stop their cancer from spreading.

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Our scientists helped to discover the BRCA gene over 25 years ago and since then we’ve led the way in developing PARP inhibitors to treat cancers with BRCA gene faults. It’s really exciting to hear about a new mutation, which behaves like the BRCA1 mutation and could in the future be treated in the same way. With PARP inhibitors already widely available, there is huge potential to help people with some of the rarest and most difficult-to-treat cancers known to us. Over the past two decades, PARP inhibitors have saved thousands of lives worldwide, and it will be interesting to see if this research in the future could lead to a similar impact for people with rarer cancers.”

The research was funded by the UK Medical Research Council, Cancer Research UK, Blood Cancer UK, Leukaemia and Lymphoma NI and Great Ormond Street Hospital Children’s Charity.

Triple-drug combo could prove key weapon in fight against cancer

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

Combining three existing drugs – a commonly-used anti-epileptic, a contraceptive steroid and a cholesterol-lowering agent – could form an effective and non-toxic treatment for a range of aggressive blood cancers, a new study reveals.

The discovery by University of Birmingham scientists has led to a £1 million funding award from Blood Cancer UK to run a randomised clinical trial to test the new drug combo against another experimental agent (Danazol) in patients living with Myelodysplastic Syndromes (MDS).

Over 7,000 people in the UK have MDS and many patients die because their disease transforms into acute myeloid leukaemia (AML) – an even more aggressive blood cancer. The general outlook for AML is poor, but when AML arises from MDS it is worse.

Left untreated, AML kills patients quickly by crippling production of normal blood cells. AML is most prevalent in elderly people – many of whom cannot tolerate ‘traditional’ treatment of intensive chemotherapy because of their age and frailty.

Scientists at the University of Birmingham had already discovered that mixing bezafibrate (BEZ – cholesterol-lowering) with medroxyprogesterone acetate (MPA – contraceptive steroid) eased a range of blood cancers including AML, chronic lymphocytic leukaemia (CLL) and non-Hodgkins lymphoma.

Now clinical trials show that adding valproic acid to a low-dose combination of the other two drugs offers enhanced killing of AML cells – giving the low-dose triple-drug combo (VBaP) a cancer-busting impact similar to a high dose of BEZ and MPA (BaP).

Researchers from the University of Birmingham have published their findings in British Journal of Cancer.

Co-author Professor Chris Bunce, commented: Using existing drugs to treat conditions outside of their approved indications is a proven approach to generate effective low-toxicity therapies. We believe that treating patients earlier with low toxicity therapies is the most effective clinical strategy for improving patient outcomes.”

Earlier clinical trials had shown that low-doses of BaP given to patients who could not have chemotherapy produced no toxic side effects and helped patients to boost their production of blood cells.

However high doses of the dual combo were not well tolerated, due to the frail nature of the patients caused by their age, poor kidney function, disease and, in some cases, prior chemotherapy treatments.

Co-author Dr Farhat Khanim commented: “A major challenge in our previous BaP trials has been the focus on elderly patients for whom more intensive therapies were not option.

“For many of these patients there are very few treatment options other than regular transfusions to combat life-threatening deficits in red cells and platelets and antibiotic control of frequent life threatening infections.

“It is therefore an attractive option to consider testing VBaP in MDS patients. As the drug combination may have profound impact on quality of life and survival of these patients.”