Author: Louise Stanley

UHB launches mRNA cancer vaccine trial for colorectal cancer

Written by Louise Stanley on 09/05/2023. Posted in Cancer outcomes, Clinical trials, Experimental medicine.

BHP founder-members University Hospitals Birmingham NHS Foundation Trust (UHB) has become the UK’s first site to launch the BioNTech Messenger RNA (mRNA) cancer vaccines trial which aims to recruit 10,000 people across the UK.

Launching within the NIHR Clinical Research Facility (CRF) at Queen Elizabeth Hospital Birmingham, mRNA vaccines are one of the most exciting experimental developments to emerge from the COVID-19 pandemic – with strong indications that they could become powerful anti-cancer treatments.

Traditionally, vaccines use dead or weakened viruses to stimulate the immune system into recognising or creating harmless antibodies, so when exposed to the real virus, the body is better placed to fend off an overwhelming infection. mRNA is a genetic material that copies instructions found in DNA, using them to make proteins that carry out functions in the body.

Efficiency and speed are part of the appeal of mRNA vaccines. The manufacture of traditional inactivated virus vaccines takes months as scientists are required to grow these on a huge scale, inactivate the virus, and then formulate it to administer in the general population. mRNA vaccine manufacture only requires the right sequence of genetic instructions.

At UHB, this mRNA trial aims to recruit patients with high-risk stage II and stage III colorectal cancers where there is no standard of care treatment to offer the patient following surgery. Each mRNA vaccine delivered will be personalised to the individual patient.

Around 42,900 people are diagnosed with colorectal cancers in the UK each year. It is the 4th most common cancer in the UK. In Birmingham and Solihull alone, almost 700 people are diagnosed with a colorectal cancer each year.

Dr Victoria Kunene, Consultant Oncologist and Principal Investigator for the trial at UHB, said: “I am really very excited that we have been able to lead the way in setting up this arm of the trial, and am looking forward to being part of the wider vaccine program at UHB.

“We are proud to have an impressive team aptly capable of safely delivering these studies here in the West Midlands, and it is a real pleasure to be part of this transformational trial.”

Prof Simon Ball, Chief Medical Officer, said: “A diagnosis of cancer is devastating for patients and their families; this trial represents a monumental step forward in providing not just hope, but a real promise of delivering better outcomes for patients with colorectal cancer, for whom there is not always a standard of care treatment available following surgery.

“Our research teams, supported by the NIHR, have a proven, distinguished track record in delivering vital trials that make significant contributions to medical and scientific discovery with the patient at the very heart; we’re immensely proud to be able to play a strong part in this here in the West Midlands.”

Participants randomised to receive the study treatment will receive 15 treatments of over one year, followed up for at least 36 months. The treatment is, in essence, a personalised medicine for post-operative patients with high-risk stage II/III colorectal cancer, for whom there is no standard of care treatment and involves the development and testing of an individualised cancer treatment called RO7198457.

UHB is the first site open for this trial – a multi-site, open-label, Phase II, randomized, controlled trial to compare the efficacy of RO7198457, versus watchful waiting in resected, Stage II (high risk) and Stage III colorectal cancer patients who are ctDNA positive following resection.

‘Individualised’ means that the treatment is made individually for each participant according to their unique cancer. This is then tested for mutations which create a unique fingerprint. The goal of an individualised cancer treatment approach is to help train the immune system to recognise and attack cancer cells.

Participants who are randomised to the observation group will be followed up for at least 48 months and visit the research site every three months. Care is provided to ensure safety during trial participation, including an informed consenting process, regular follow up where biomarkers and all reported outcomes are collected and analysed.

Incurable blood cancer trial finds new drug better than current treatments

Written by Louise Stanley on 05/05/2023. Posted in Cancer outcomes, Clinical trials.

Patients with an incurable blood cancer – polycythaemia vera (PV) – may respond better to a new drug compared to conventional best treatment, a new clinical trial has found.

The rare cancer results in patients producing too many red blood cells and the drug, Ruxolitinib, has been found to be better at treating PV compared to the best currently available treatment. Researchers at BHP founder member the University of Birmingham – funded by Blood Cancer UK – looked at how well the drug worked in those who don’t respond well to the first line of treatment in a randomised phase-II clinical trial.

In this trial, dubbed MAJIC-PV, 39 different hospitals co-ordinated by Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU) recruited 180 people with PV. They compared ruxolitinib (a drug that targets JAK2 and is already approved for use in PV but not available in the UK) with currently available therapies. Ruxolitinib led to better control of the disease with normal blood counts and a reduced spleen size.

For the first time ever, using samples from the study, the researchers showed that both controlling the blood count and reducing mutated JAK2 by 50% led to fewer disease related events – and that those patients with reduction in JAK2 mutation lived longer, with lower risk of disease progression.

Professor Pamela Kearns, Director of the CRCTU at the University of Birmingham said: “Working on new treatments for incurable cancers is just the kind of thing that the Birmingham Cancer Research UK Clinical Trials Unit is about. I am really pleased that this important clinical trial has found that ruxolitinib has long-term clinical benefit for the ongoing treatment of patients with PV, and that further trials will be able to identify whether the drug can be used as an effective first line treatment.”

PV belongs to a group of conditions that affect the blood called myeloproliferative neoplasms (MPNs). Recently Tim Jonze from the Guardian and ex-radio one DJ David Hamilton have announced they have this form of blood cancer, raising awareness of this lesser-known disease.

The disease is caused by a mutation in a gene called JAK2 and can cause blood clots. Those living with the disease have a risk of a reduced life expectancy as well as development of more aggressive blood cancers including myelofibrosis and acute leukaemia.

One of the commonly used treatments is a drug called – hydroxycarbamide – but those whose cancer does not respond to this drug have a poor prognosis.

Professor Claire Harrison, consultant haematologist at Guy’s and St Thomas’ NHS Foundation Trust and the trial lead, said: “For some time we have wanted to be able to understand the long-term benefits of a drug such as ruxolitinib for patients with PV. This study shows several important messages about this therapy which will hopefully shortly be available for UK patients. These are that comprehensively controlling the blood count reduces disease related events, and that molecular monitoring of mutation levels may also begin to be important.

“Patient therapy is chosen on an individual basis but options have hitherto been limited for PV patients. We are now studying this drug for newly diagnosed patients in a world-first study MITHRIDATE. I would like to thank all the patients who volunteered to be part of this study, their families, UK research teams, Novartis which provided the drug and Blood Cancer UK which funded the trial infrastructure and the trial management team.

Dr Suzanne Rix, Research Funding Programme Manager at Blood Cancer UK, said: “Blood cancer is the fifth most common cause of cancer in the UK, affecting over a quarter of a million people. There is currently no cure for polycythaemia vera and there are a number of complications that can arise from it, so designing, developing and testing medicines to give patients the best outcome possible is vitally important.

“Blood Cancer UK is committed to funding excellent quality scientific research to ensure we deliver better treatments for blood cancer, faster. This trial is a great example of how collaboration between charities, academia, clinicians and pharmaceutical companies can deliver impactful results.

“Our heartfelt thanks go out to those who took part in the trial, without whom we wouldn’t have been able to collect this vital information and continue to improve the outcomes for people with blood cancer.”

Second city’s strategic health alliance welcomes mental health trust as new member

Written by Louise Stanley on 02/05/2023. Posted in Birmingham Health Partners, Mental health.

Birmingham Health Partners has underlined its commitment to delivering research that enhances health and wellbeing by welcoming Birmingham and Solihull Mental Health NHS Foundation Trust (BSMHFT) as its fifth NHS member.

BSMHFT was founded in 2003 and provides a wide range of inpatient, community and specialist mental health services – including early intervention and rehabilitation – and is one of the largest mental health trusts in the country with a workforce of around 4,000 across 50 sites. With a national and international reputation for research, BSMHFT maintains strong academic links with a number of prestigious institutions including BHP members the University of Birmingham and Aston University, and its portfolio includes studies focused on dementia, eating disorders, addictions, mood disorders and perinatal mental health.

Roisin Fallon Williams, Chief Executive of BSMHFT, commented: “My colleagues and I welcome the opportunities that membership of Birmingham Health Partners will provide to both our service users and our Trust, through the benefits of continued research and innovation in provision of mental health care in our region. We believe passionately that research is complementary to service delivery, rather than surplus to it, and BHP’s ethos of embedding research into all stages of clinical care is a perfect fit with our own culture.”

Professor David Adams, Director of BHP, commented: “BHP’s mission is to work collaboratively to ensure our community are ‘born well, live well, and die well’. The importance of mental health and wellbeing to this vision cannot be overstated, and neither can the intrinsic link between physical and mental health be overlooked. BSMHFT is already a long-term partner in many of the mental health studies and trials run across BHP, and so their formal inclusion in our partnership is a natural extension of our collaborations to date.”

BHP’s membership now comprises: the University of Birmingham; Aston University; Birmingham and Solihull Mental Health NHS Foundation Trust; Birmingham Women’s and Children’s NHS Foundation Trust; the Royal Orthopaedic Hospital NHS Foundation Trust; Sandwell and West Birmingham Hospitals NHS Trust; University Hospitals Birmingham NHS Foundation Trust; and the West Midlands Academic Health Science Network.

‘Vein-on-a-chip’ could help scientists study blood clots without animal models

Written by Louise Stanley on 28/04/2023. Posted in Experimental medicine.

Blood clot researchers could benefit from a new device that mimics a human vein, replacing the need for animals for some studies.

The vein-on-a-chip model has been developed by scientists at BHP founder-member the University of Birmingham, and can be used in experiments to understand mechanisms of blood clot formation in conditions such as deep vein thrombosis (DVT).

DVT is the development of blood clots in veins, usually in the legs. It is a serious condition because the clot can detach and travel to the lungs, where it may block blood vessels, causing breathing difficulties that prove be fatal. DVT is the third most common cardiovascular disease after myocardial infarction and stroke, with tens of thousands of people in the UK developing this condition every year. Mechanisms of deep vein thrombosis require further research to improve clinicians’ understanding and ability to treat or prevent the condition.

The new device, described in a recent paper published in Frontiers in Cardiovascular Medicine, is a tiny channel, which includes structures called valves that ensure the correct direction of blood flow.

UoB researchers Dr Alexander Brill from the Institute of Cardiovascular Sciences, together with Drs Daniele Vigolo and Alessio Alexiadis from the School of Chemical Engineering, led the development of the new device.

Dr Brill said: “The device is more advanced than previous models because the valves can open and close, mimicking the mechanism seen in a real vein. It also contains a single layer of cells, called endothelial cells, covering the inside of the vessel. These two advances make this vein-on-a-chip a realistic alternative to using animal models in research that focuses on how blood clots form. It is biologically reflective of a real vein, and it also recapitulates blood flow in a life-like manner.

“Organ-on-a-chip devices, such as ours, are not only created to help researchers move away from the need for animal models, but they also advance our understanding of biology as they are more closely representative of how the human body works.

“The principles of the 3Rs – to replace, reduce and refine the use of animals in research – are embedded in national and international legislation and regulations on the use of animals in scientific procedures. But there is always more that can be done. Innovations such as the new device created for use in thrombosis research are a step in the right direction.”

This research was funded by the NC3R, British Heart Foundation and Wellcome.

Drug combination could overcome tumour resistance in paediatric cancers

Written by Louise Stanley on 21/04/2023. Posted in Cancer outcomes, Clinical trials.

Children with some solid tumours may benefit from receiving a combination of inhibitor drugs, according to interim results of research presented at the American Association of Cancer Research’s Annual Meeting 2023, held April 14-19.

The ongoing research being conducted by an international team including the University of Birmingham suggests that a combination of the PARP inhibitor olaparib (Lynparza) and the investigational ATR inhibitor ceralasertib showed clinical benefit in paediatric patients with solid tumours exhibiting DNA replication stress and/or DNA repair deficiencies.

Dr Susanne Gatz, associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham presented the study.

Dr Gatz said: “To our knowledge, the combination of PARP inhibitors and ATR inhibitors has not been widely investigated in adult tumour types. This is the first proof of principle that the combination is well tolerated and can lead to clinically relevant responses in paediatric cancers.”

AcSé-ESMART is an international European proof-of-concept platform trial intended to match paediatric, adolescent, and young adult patients with relapsed or treatment-refractory cancers with a treatment regimen targeted to their cancer’s mutational profile. Gatz and colleagues, including Birgit Geoerger, MD, PhD, head of the AcSé-ESMART trial, have so far evaluated 15 different treatments, mostly combination strategies, in more than 220 children following mandatory high-throughput genomic profiling of their tumours.

Arm N of AcSé-ESMART is tailored toward patients with malignancies that exhibit defects in DNA replication and damage repair. Impairments in homologous recombination (HR), a type of DNA repair, can sensitize cells to drugs called PARP inhibitors. PARP inhibitors have proven effective against specific adult cancers with HR deficiencies—most notably, mutations in BRCA1 or BRCA2. How to best use PARP inhibitors in paediatric patients where BRCA1/2 mutations are rarely found remains unclear.

Dr Gatz said: “Paediatric cancer cells proliferate rapidly and have some element of replication stress and a dependency on ATR. We think there might be a kind of primary resistance of paediatric cancers to PARP inhibitors and that combination with an ATR inhibitor could potentially overcome that.”

Gatz also explained that paediatric cancers are often driven by complex mechanisms, making it difficult to identify an effective treatment regimen. Single-agent therapies targeting one mutated protein are often insufficient in paediatric patients, necessitating additional research into combination therapies and mechanisms of response.

“So far, it is unclear if the molecular alterations based on which the patients were enrolled in this trial are the sole reasons for response,” Gatz said.

“Further, it may be difficult to identify patterns of response in specific tumour types due to the tumour-agnostic nature of the study. Nevertheless, this study design can give preliminary indications of signals in specific alterations and tumour types and can provide the basis for future clinical trials.”

Gatz and colleagues plan to evaluate biomarkers of response from the raw sequencing data of the enrolled patients, from the expression of key target proteins such as ATM, and from RNA sequencing data.

Gatz noted that these analyses may identify “molecular constellations” indicative of response to olaparib plus ceralasertib.

“There are enormously valuable drugs currently in development and, provided there is a good clinical or preclinical rationale, we need to apply them more creatively to diseases for which the drug is not currently indicated,” Gatz said.

Limitations of this study include a small, non-randomized sample intended primarily as a proof of concept and to determine the optimal dose for study expansion.

The study is as yet unpublished.

West Midlands Innovation Accelerator to Spark Growth and Innovation

Written by Louise Stanley on 21/03/2023. Posted in Birmingham Health Partners.

The Universities of Birmingham and Aston – both BHP members – are to participate in the West Midlands Innovation Accelerator announced this week by the West Midlands Combined Authority.

Designed to bolster the region’s innovation and R&D capability, as well as sparking commercial growth and investment, the Innovation Accelerator will receive a share of a new £100m fund from Innovate UK. This fund, first announced in the Government’s 2022 Levelling up White Paper, will be divided across three regional Innovation Accelerators over the next two years.

Aims of the Innovation Accelerator include accelerating the region’s engineering research & development, boosting inward investment, and reinforcing the West Midlands’ position at the frontier of the UK innovation revolution by enabling businesses to develop new products, processes and services.

The West Midlands Innovation Board has targeted investment on five projects enabling new solutions around Medical and Clean Technologies.

The University of Birmingham is leading the 6D Innovation Accelerator project, bringing together key stakeholders (universities, hospitals, industry and government-funded ‘Catapults’ for manufacturing innovation) to supercharge the region’s ability to accelerate new health and medical technologies. Its aim is to deliver a streamlined programme to help companies navigate “pinch-points” in the process of medical translation.

Professor Liam Grover, of the University of Birmingham’s Healthcare Technologies Institute, said: “Taking health and medical technologies into the market place can be a minefield of regulatory, funding and management issues. We aim to develop clear processes that will help companies navigate the obstacles and deliver marketable products that will enhance people’s lives.”

The 6Ds are:

- - Diagnosis of company needs
  - Definition of major NHS and industry-based challenges to target
  - Development and refinement of prototype products
  - Deployment of innovation in real-world NHS settings
  - Diversification of supply chains, skills and services
  - Demonstration of significant economic and health benefits for our region

The University is also playing a key role in a second project, Digital Innovation Transformative Change (DIATOMIC), led by Connected Places Catapult, the UK’s innovation accelerator for cities, transport and place leadership. Partners include Aston University, Birmingham City Council, Birmingham City University, Greater Birmingham Chambers of Commerce.

DIATOMIC will accelerate place-based innovation in the West Midlands. Harnessing the region’s existing international relationships and through a series of targeted initiatives, it will focus on growing the region’s clean tech, health tech and med tech markets.

Through DIATOMIC civic leaders will be able to set innovation challenges, support local SMEs to respond and benefit the community through the UK’s first inclusive innovation hub. It will also promote the use of data to enable better place-based decision making and develop an impact assessment toolkit.

Announcing the Innovation Accelerator, Andy Street, Mayor of the West Midlands, and chair of the WMCA, said: “I’m delighted to see the Innovation Accelerator fund finally land in our region which will unlock a further £150m of private sector co-investment. The funding will inject momentum into the delivery of the West Midlands Plan for Growth which sets out how we will unlock hundreds of thousands of new jobs and be home to major global companies in this decade.

“One of my key mayoral missions is to restore our status as the fastest growing region outside of London – just as we were pre-pandemic. Innovation is central to achieving that mission.

“We’re already a leading region for UK innovation when it comes to automotive and aerospace – with every £1 of Government spending for Research & Development translating in to £4 of business investment. This latest news will help us to build on our progress to date – with Government’s forthcoming Trailblazer Devolution Deal and proposed programme of Investment Zones set to usher in exciting times ahead.”

Minister of State for Science Research & Innovation at DSIT George Freeman said: “Through Record investment in our UK science, technology & innovation sectors, the Innovation Economy is creating new career opportunities in the campuses, clusters & companies of tomorrow.

“That’s why UKRI is putting clusters at the heart of its of its £25bn budget up to 2025, and why our £100m Innovation Accelerator Program provides £33m each to 3 emerging clusters to attract industrial co-investment and become major, globally competitive centres for research and innovation.

“The West Midlands Cluster is becoming a world class hub of R+D in med tech and clean tech.

“I’m delighted that local leaders have come together to use our £33m to launch such exciting programs with industry and Universities in this exciting area.”