Posts

Early Detection Award for research into the clinical application of single cell genomics

Myelodysplastic syndromes (MDS) are a group of blood cancers in which the bone marrow fails to make normal levels of blood cells. MDS can be broadly classified into two major groups: high-risk MDS, in which patients progress to acute myeloid leukaemia with a very poor survival rate; and low-risk MDS, in which the disease is less aggressive but patients still suffer from a huge burden of symptoms, often the result of anaemia.

There are a number of exciting new targeted treatment options for low-risk MDS. However, these do not work in all patients and, particularly given the high economic cost of newer treatments, current biomarkers are not sufficiently predictive of treatment response. There is a need to more precisely categorise MDS to predict the disease trajectory and the response to therapy so that the most effective treatment can be given to each patient.

Large investments in sequencing technology in clinical laboratory services are enabling precision medicine in certain cancers and revolutionising patient care. Dr Onima Chowdhury, MRC Clinical Academic Research Fellow and Consultant Haematologist (MRC Weatherall Institute of Molecular Medicine and Oxford University Hospitals) is working with Professor Adam Mead, Dr Supat Thongjuea and Dr Lynn Quek at the MRC WIMM to explore the use of single-cell genomics in the clinical diagnosis and management of MDS. Funded by a Cancer Research UK Early Detection and Diagnosis Primer Award, the team will seek to develop a simple, clinically applicable processing and analysis pipeline, as well as identifying biomarkers that correlate and can perhaps supersede current diagnostic modalities.

Long-term, the team hope that this approach will be able to improve outcomes of patients through improved diagnosis, risk prediction and targeted treatment in MDS and other haematological malignancies.

New funding for early diagnosis research using platelets

It is known that the earlier a cancer is detected, the more likely a cancer patient is to have better outcomes. One of the challenges for achieving early detection is to develop a minimally invasive test to detect the signs of early cancer in the body.

Because blood tests are simple to carry out in the clinic, a lot of effort has been focused on detecting molecules released from cancer cells in blood samples – so-called ‘liquid biopsies’. However, the majority of techniques that are used currently have a low sensitivity for early-stage cancers, due to low levels of cancer cell-derived molecules being present in blood plasma.

Dr Bethan Psaila, Cancer Research UK (CRUK) Advanced Clinician Scientist, Group Leader at the Medical Research Council Weatherall Institute of Molecular Medicine (MRC WIMM) and principal investigator at the Radcliffe Department of Medicine at Oxford University, is pioneering an approach that might be able to enrich for cancer-derived molecules in the blood. Working with Professor Chris Gregory (University of Edinburgh), Professor Paul Rees (University of Swansea) and Dr Henkjan Gersen (University of Bristol), Beth is leading a multi-disciplinary team that brings together cancer cell biologists, and imaging and engineering expertise to explore the use of platelets for early cancer diagnosis.

Platelets perfuse tumours and take up cancer cell-derived biomolecules. Isolating platelets from the blood and analysing their contents will hopefully be a more sensitive method for detecting cancer-specific molecules in the blood.

In this newly funded project, the team will use state-of-the-art pre-clinical models as well as samples from patients with colorectal cancer, pancreatic cancer and oesophageal cancer as exemplar cancers to assess the utility of ‘tumour-educated’ platelets (TEPs) for early cancer diagnosis. They will use detailed imaging and biomechanical techniques to assess whether TEPs can be reliably distinguished from platelets in healthy people or those with non-malignant disorders.

This multi-institutional project is funded by a Cancer Research UK Early Detection and Diagnosis Project Award and builds on a successful CRUK Innovation Award the team received after a workshop on liquid biopsy technologies in 2018. The ~£650,000 award will run for four years and will support two DPhil studentships, a postdoctoral research scientist and a research assistant.

Novel imaging device enters first round of development funding programme

Proton-beam-therapy (PBT) is becoming increasingly important for treating cancer, with projected increases of up to 50% more patients per year being treated with the technology in the UK and worldwide by 2025.

Although the precision of PBT has many advantages over traditional radiotherapy, there some uncertainty over the range of delivery the beam provides. There is risk of potential overdose to normal tissues or underdose to tumour, resulting in reduced tumour-control and long-term side-effects due to treatment of healthy tissue. This can be detrimental to patients and a burden on healthcare systems if side-effects become apparent later in a patient’s life.

Therefore, a method to verify the range of treatment beams when using PBT on patients is crucial to increase the treatment accuracy. Dr Anna Vella, Postdoctoral with the Radiation Therapy Medical Physics Group, led by Prof. Frank Van Den Heuvel, at the University of Oxford’s Department of Oncology, is investigating the efficacy of a device with this purpose.

Anna is leading CAPULET (Coded Aperture Prompt-gamma Ultra-Light imaging detector), an imaging device for quality assurance assessment of radiotherapy plan efficacy, designed for daily use in clinical practice. CAPULET could be installed onto a variety of PBT devices, and used to verify and fine-tune the dose between fractions in particle-beam radiotherapy. It does this through collecting 3D images of the particle beam penetrating soft-tissue, with the ultimate goal to fine-tune planning doses and improving the efficacy of the overall radiotherapy treatment.

This novel and unique technology is faster & more compact than current devices, increases the field-of-view, and improves the signal-to-noise ratio. The impact on patients will be to improve cancer-control, fewer complications, and improved quality-of-life following treatment.

CAPULET has recently been selected as one of 35 projects in the Pre-Development Phase of the Alderley Park Oncology Development Programme – a national programme designed to develop and progress start-up oncology projects. Funded by Innovate UK and Cancer Research UK. It will now be work-shopped, and potentially be chosen to join the full development programme with grant funding.

Proof-of-concept experiments will be performed in collaboration with the CRUK-funded ART-NET. The long-term plan of CAPULET is to develop a large-area detector to fully image the beam delivery range within lungs, liver, H&N and other large sites in the human body to overcome limited field-of-view found in other existing devices on the market.

Funding to improve childhood, teenage and young adult cancer detection

Cancer is the commonest cause of death among children and young people in the UK and is associated with significant long-term morbidity. Unfortunately, the UK lags behind other high-income countries in the time it takes to diagnose childhood, teenage and young adult (TYA) cancer and this delay worsens patient outcomes.

One of the challenges in diagnosing childhood and TYA cancer is its relative rarity and non-specific presentation, and awareness campaigns have been run in an effort to improve recognition of cancer signs among health professionals. Although this resulted in improvements for certain types of cancers in children and TYA, the national time-to-diagnosis targets have still not been reached in all cancers for all age groups.

Dr Defne Saatci and Professor Julia Hippisley-Cox (Nuffield Department of Primary Care Health Sciences) have successfully applied for a Cancer Research UK Early Detection and Diagnosis Project Award to accelerate diagnosis of childhood and TYA cancer. They will use the QResearch database, the UK’s largest GP electronic health record database, covering 20% of the UK population and linked to national cancer, hospital and mortality registries. QResearch data will be explored to identify the early symptoms and signs associated with a subsequent diagnosis of the commonest childhood and TYA cancers (acute lymphoblastic leukaemia, lymphomas and central nervous system tumours) and this information will be used to develop a risk prediction tool for GP use.

By increasing the understanding about the clinical features associated with childhood and TYA cancers and developing this risk prediction tool for use in primary care, this study aims to make significant advancements in childhood and TYA cancer diagnosis and outcomes.

If you are an Oxford-based researcher thinking of applying for external early detection funding, please get in touch with the OxCODE Scientific Coordinator who can help to coordinate your application.

 

New Oxford spin-out Singula Bio launches

Singula Bio is a bold new seed-stage biotechnology company spun out of Oxford University. It aims to become a world leader in developing neoantigen-based individualised cell therapies to use against difficult-to-treat solid malignancies such as ovarian cancer.

This patient-centred approach will pioneer immunological, medical, surgical and computational technologies to generate selective therapies that eliminate cancer, and the ultimate hope is to achieve long-term, high-quality disease-free survival for cancer patients.

Singula Bio was co-founded by Professors Ahmed Ahmed, Enzo Cerundolo and Enda McVeigh from the Nuffield Department of Women’s & Reproductive Health at Oxford University. It is supported by Oxford University Innovation (OUI), the University’s research commercialisation company, and it has secured generous seed-stage investment from IIU Nominees Limited to pursue its goals. Singula Bio is a landmark for OUI as it is the 250th OUI-supported venture to have passed through the office since it opened its doors in 1987.

Motivated by their many patients (and laboratory funding from charities Ovarian Cancer Action and Cancer Research UK) Profs Ahmed and Cerundolo were inspired to improve an individual’s gruelling experience of cancer and to lessen their suffering of other treatments. Together, they have an enormous knowledge in cancer medicine, cancer immunology, cell and molecular biology, and computational biology which has enabled them to design patient-specific cancer cell therapies that harness the power of the patient’s own immune system to fight cancer.

In a tumour, cancer cells carry mutations that appear foreign to a patient’s body and, therefore, their immune system reacts to these mutations. One strong form of an immune reaction is through generating mutation-specific cells called “T cells”.

Prof Ahmed, Professor of Gynaecological Oncology at the Nuffield Department of Women’s & Reproductive Health, Oxford University, said:

“A key feature of cancer cells is the preponderance of genetic aberrations in their DNA. These aberrations can make proteins appear foreign to our body’s immune system which then develops immune cells (T cells) to fight cancer cells. Thanks to years of research and technology development we now know how to identify relevant tumour-specific T cells to grow them outside the body and deliver them back to patients to fight cancer cells.”

Studying viral genetics to aid liver cancer early detection

Chronic Hepatitis C virus (HCV) infection causes liver damage and is a significant risk factor for liver cancer. There are now cures available for chronic HCV infection and the World Health Organisation has set a target to eliminate HCV by 2030. However, although curing HCV reduces the risk of liver cancer, individuals with a history of chronic HCV infection remain at higher risk.

There are multiple types of HCV that differ in their genetic sequences. Previous research has established that not all HCV genotypes present the same level of risk for liver cancer. The next step is to discover which particular viral genetic motifs are most associated with liver cancer so the HCV-infected individuals who are at the highest risk of liver cancer can be identified. This will enable more targeted surveillance to detect liver cancer earlier when treatment is more likely to be successful.

Professor Ellie Barnes and Dr Azim Ansari (Nuffield Department of Medicine) have been awarded funding as part of a wider Wellcome Trust Collaborative Award led by Professor Graham Foster (Queen Mary’s University, London) to study anti-viral drug resistance and long-term effects of HCV in Pakistan. HCV infection is highly prevalent in Pakistan with up to 20% of the population infected in hotspot regions.

A cohort of ~500 individuals with HCV-associated liver cancer will be recruited and samples will be collected for viral whole genome sequencing. The Oxford team will then analyse these sequences, comparing to people with HCV infection but not cancer, to identify any genetic patterns that are linked to cancer.

This work complements the recently launched Cancer Research UK-funded DeLIVER programme which, among other features, will study host and viral genetics in a cohort of individuals with HCV and liver cancer in the UK.

Christina Ye awarded CRUK pre-doctoral fellowship

Immune related toxicity is a common side effect of treatment with Immune Checkpoint Blockers for cancer – but the degree to which the development of these side effects is related to overall oncological outcome is unclear. As an Academic Foundation Programme Trainee within OUCAGS (https://www.oucags.ox.ac.uk), I had a four month block of time to work in a lab to gain experience of research. I worked with Dr Benjamin Fairfax’s group in the WIMM/Department of Oncology to explore the relationship between immune toxicity and clinical outcomes. Working with other members of the group, and Dr Anna-Olsson Brown in Liverpool, we found that patients who developed immune related toxicity appeared to have better long-term clinical outcomes including overall survival. Indeed, we found the development of toxicity was a key predictor of the cancer responding to treatment. This work is currently in-press in the British Journal of Cancer.

This period of time in the lab stimulated my interest in research and helped in my decision to apply for an Academic Clinical Fellowship in Dermatology. I was successful in this and I have a further nine months of protected research built into my training this year, which I again plan to spend working in Ben’s group. As a trainee dermatologist I am particularly intrigued by the rash patients frequently develop when they first receive immunotherapy. There is evidence to suggest that another side effect of immunotherapy, colitis, is secondary to the activation of resident memory T cells. Conversely, when you look at the gene expression in CD8 T cells after treatment with checkpoint blockers you can see up-regulation of genes involved in skin trafficking. I will explore whether this rash is indicative of T cell trafficking to the skin, or activation of resident memory T cells, or something completely separate.

Cancer Research UK awards biannual pre-doctoral research bursaries, aimed at providing ‘short term funding to allow clinicians and other health professionals to get involved in research projects early in their career’. Ben encouraged me to apply to this CRUK scheme to further explore the mechanistic basis of the rash in immunotherapy and I am very grateful to have been awarded this funding. Personally I am hoping to gain training in immunological techniques and bioinformatic analysis during this period, and I hope the results we generate will provide further insights into the cells cancer immunotherapy affects and how it works.

Funding boost for OxPLoreD early detection study

OxPLoreD is an observational cohort study sponsored by Johnson and Johnson that will recruit 1650 patients from across the UK with pre-cancerous lymphoproliferative disorders. These conditions include monoclonal B-cell lymphocytosis and monoclonal gammopathy of unknown significance that put individuals at higher risk of developing the blood cancers chronic lymphocytic leukaemia and multiple myeloma respectively.

The aim of the study is to look for new ways to find and treat blood cancer sooner by identifying clinical, genomic and immunological predictive markers of progression from these pre-cancerous conditions to malignant disease. The study will also explore the possibility of a future early intervention trial for the subgroup of patients at highest risk of progression.

OxPLoreD is one of the seven clinical trials that have received an £8m funding boost from UK Research and Innovation (UKRI) and will work in partnership with Genomics England. The funding will speed up the adoption of whole genome sequencing in the study of cancer. Genetic analysis is a critical tool that can allow clinicians to select the most appropriate treatments for each patient. In the OxPLoreD study, genetic analysis might be able to identify individuals at highest risk of disease progression that would benefit from earlier treatment. In the longer term this may also enable the identification of those people who would benefit from certain types of treatment.

Alison Cave, UKRI challenge director says:

“Research tells us that one-in-two people in the UK population will get cancer. That stark statistic shows just how important it is for us to seek new treatments. The use of genetic analysis opens new possibilities in our drive to beat cancer. The projects for which we have announced funding today are exciting pointers to future diagnosis and precision treatments”

The funding has been delivered through UKRI’s Industrial Strategy Challenge Fund’s £210m data to early diagnosis and precision medicine (DEDPM) programme. The challenge aims to combine research data and evidence from the NHS to create new and improved ways of identifying disease and treatment pathways.

Prof. Sir Mark Caulfield, Chief Scientist at Genomics England says:

“The 100,000 Genomes Project, Genomics England has analysed the genomes of over 17,000 cancer participants and this suggests that up to half have revealed mutations of potential clinical significance. The DEDPM programme is a major opportunity to expand the application of whole genome sequencing into clinical trials involving cancer where support from the ISCF is likely to deliver significant clinical benefit”

For more information about the other trials funded by this scheme, see the UK Research and Innovation announcement.

Oxford to lead new programme of AI research to improve lung cancer screening

UK Research and Innovation, Cancer Research UK and industry are investing more than £11 million in an Oxford-led artificial intelligence (AI) research programme to improve the diagnosis of lung cancer and other thoracic diseases.

Professor Fergus Gleeson at the University of Oxford will lead on a programme of research focusing on accelerating pathways for the earlier diagnosis of lung cancer. Lung cancer is the biggest cause of cancer death in the UK and worldwide, with £307 million/year cost to the NHS in England. The earlier that lung cancer is diagnosed, the more likely that treatment will be successful but currently only 16% patients are diagnosed with the earliest stage of the disease. To address this clinical problem, NHS England is launching a £70 million lung cancer screening pilot programme at 10 sites*.

To improve patient care beyond the current screening guidelines, a team of academics from Oxford University, Nottingham University, and Imperial College London; NHS clinicians from Oxford University Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, the Royal Marsden Hospital, the Royal Brompton Hospital, and University College London Hospitals NHS Foundation Trust; and the Roy Castle Lung Cancer Foundation will join forces with three leading industrial partners (Roche Diagnostics, GE Healthcare, Optellum).

Working with the NHS England Lung Health Check programme, clinical, imaging and molecular data will be combined for the first time using AI algorithms with the aim of more accurately and quickly diagnosing and characterising lung cancer with fewer invasive clinical procedures. Algorithms will also be developed to better evaluate risks from comorbidities such as chronic obstructive pulmonary disease (COPD). In addition, this programme will link to data from primary care to better assess risk in the general population to refine the right at-risk individuals to be selected for screening. It is hoped that this research will define a new set of standards for lung cancer screening to increase the number of lung cancers diagnosed at an earlier stage, when treatment is more likely to be successful.

Professor Fergus Gleeson, Chief Investigator for the programme, said

“The novel linking of diagnostic technologies, patient outcomes and biomarkers using AI has the potential to make a real difference to how people with suspected lung cancer are investigated. By differentiating between cancers and non-cancers more accurately based on the initial CT scan and blood tests, we hope to remove the delay and possible harm caused by repeat scans and further invasive tests. If successful, this has the potential to reduce patient anxiety and diagnose cancers earlier to improve survival and save the NHS money.”

This programme builds on the National Consortium of Intelligent Medical Imaging (NCIMI) at the Big Data Institute in Oxford, one of five UK AI Centres of Excellence. The funding, delivered through UK Research and Innovation’s (UKRI’s) Industrial Strategy Challenge Fund, is part of over £13m government investment in ‘data to early diagnosis and precision medicine’ for the research, development and evaluation of integrated diagnostic solutions. UKRI is also partnering with Cancer Research UK, which is making up to a £3m contribution to the cancer-focused projects. The Oxford-led project is one of six awarded from this competition.

Science Minister, Amanda Solloway MP, said:

“Our brilliant scientists and researchers in Oxford are harnessing world-leading technologies, like AI, to tackle some of the most complex and chronic diseases that we face. Tragically, we know that one in two people in the UK will be diagnosed with some form of cancer during their lifetime. The University of Oxford project we are backing today will help ensure more lives are saved and improved by using state of the art technology to identify cancerous tumours in the lung earlier and more accurately.”

Dr Timor Kadir, Chief Science & Technology Officer at Optellum Ltd, commented:

“Three industry leaders – Roche, Optellum and GE – have joined their expertise in molecular diagnostics, imaging and AI to help diagnose and treat lung cancer patients at the earliest possible stage. The programme results will be integrated into Optellum’s AI-driven Clinical Decision Support platform that supports physicians in choosing the optimal diagnostic and treatment procedures for the right patient at the right time.”

Ben Newton, General Manager, Oncology, at GE Healthcare, said:

“We are very pleased to be working with the University of Oxford via the NCIMI project on this important lung cancer research. By extending our existing NCIMI data infrastructure and creating innovative AI solutions to spot comorbid pathologies, we aim to help identify lung diseases earlier in the UK.”

Geoff Twist, Managing Director UK and Ireland and Management Centre European Agents at Roche Diagnostics Ltd, said:

“We are thrilled with this funding award, because it gives us the opportunity to work towards ground-breaking innovation in early diagnosis and because working in partnership is vital to achieve success in the health system. By bringing together the collective knowledge and expertise of these academic, medical and industry partners, this project has the potential to impact patient care globally through new diagnostic solutions in lung cancer.”

Dr Jesme Fox, Medical Director of the Roy Castle Lung Cancer Foundation, said:

“The majority of our lung cancer patients are diagnosed too late for the disease to be cured. We know that we need to be diagnosing lung cancer at an earlier stage, through screening. This innovative project has the potential to revolutionise lung cancer screening, making it more efficient and most importantly, saving lives. Roy Castle Lung Cancer Foundation is delighted to support this Programme”

Professor Xin Lu, co-Director of the CRUK Oxford Centre and Director of the Oxford Centre for Early Cancer Detection, commented:

“I am delighted that this national multi-site collaborative programme will be led from Oxford by Fergus Gleeson. Involving a world-class team of academics, clinicians, local and global industry, and patient representatives, this research is hugely important for accelerating lung cancer detection.”

 

* The 10 NHS England Lung Health Check sites are:

  • North East and Cumbria Cancer Alliance – Newcastle Gateshead CCG
  • Greater Manchester Cancer Alliance – Tameside and Glossop CCG
  • Cheshire and Merseyside Cancer Alliance – Knowsley CCG and Halton CCG
  • Lancashire and South Cumbria Cancer Alliance – Blackburn with Darwen CCG and Blackpool CCG
  • West Yorkshire Cancer Alliance – North Kirklees CCG
  • South Yorkshire Cancer Alliance – Doncaster CCG
  • Humber, Coast and Vale Cancer Alliance – Hull CCG
  • East of England Cancer Alliance – Thurrock CCG and Luton CCG
  • East Midlands Cancer Alliance – Northamptonshire CCG and Mansfield and Ashfield CCG
  • Wessex Cancer Alliance – Southampton CCG

 

NDORMS win cancer research awards

 

Nuffield Department of Orthopadics, Rheumatology and Musculoskeletal Sciences (NDORMS) supports multi-disciplinary research into the causes of musculoskeletal and inflammatory conditions, in order to improve people’s quality of life. Based within the Medical Science Division of Oxford University, NDORMS collaborates with many leading research units, particularly in the field of cancer research, to develop new and innovative ways to tackle cancer and its treatment.

Three awards have been given to NDORMS researchers for their work on cancer and its treatment. The awards include grant funding to further their work, which you can find out more about below.

Meet the winners

Audrey Gerard has been awarded the CRUK Immunology Project Award, for her research into mechanisms that inhibit anti-tumour immunity. So far, her research has had great success in the application of treating aggressive cancers, but stimulating the body’s own immune system to remove cancer cells.

This award hopes to further her research, hand help to determine if there are other aspects restricting tumour immunity that can be exploited.

Anjal Kusumble, Richard Williams and Felix Clanchy have been awarded the CRUK Early Detection Primer Award for their work on Ewing’s Sarcoma – a highly malignant tumour of the bone or surrounding tissue. This cancer is particularly hard to treat due to the difficulty of identifying and diagnosing it.

The team’s work into improving early detection of Ewing’s Sarcoma and its spread through the body has shown great promise in identifying potential relapses. The award will provide the funding needed to consolidate previous work and find new solutions to tackle the disease.

Alex Clark has been awarded the Cancer Immunology grant to support his exploration of how metabolic processes in B cells promote autoimmunity and lymphoma. The aim of this project is to find a way to interfere with the important pathways needed for cells to create amino acids – the building blocks for cell and cancer cell growth.

This work may pave the way for new treatment approaches which can be applied to diseases such as lymphoma.