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The next step in personalised cancer medicine

Researchers at the Botnar Research Centre, University of Oxford have developed technology that facilitates standalone long-read Oxford Nanopore sequencing of single cells. This breakthrough technology has the potential to open new avenues within genomics and enable future discoveries to understand the causes of many human diseases.

The work, in part supported by grants from the UKRI (Innovate UK, EPSRC and MRC), results from a collaboration with researchers from the Department of Chemistry at Oxford University, ATDBio, a world leader in complex oligonucleotide chemistry, and pharmaceutical company BristolMyersSquibbs. The study has been published in this week’s issue of Nature Biotechnology.

“The application of accurate long-read single-cell sequencing will have a transformative effect on the wider single-cell sequencing community, as longer and full-length transcriptomic sequencing allows users to capture more information about the transcriptional and functional state of a cell,” says Assistant Professor Adam Cribbs, senior author of the paper and Group Leader in Systems Biology and Next Generation Sequencing Analysis at the Botnar Research Centre. “This means that we move closer to being able to better understand and diagnose diseases such as cancer”.

Single-cell genomics, the ability to examine all information contained in an individual cell, is a rapidly evolving field and is dominated by droplet-based short-read single-cell sequencing applications. In this approach, cells are encapsulated with barcoded RNA-capture microbeads into droplets within an oil emulsion. Each droplet becomes a discrete reaction vessel, associating a different barcode with each cell’s RNA and a unique molecular identifier (UMI) with each RNA transcript.  Once barcoded, RNA from all cells can be pooled and processed conventionally for next generation sequencing.  During sequencing, both the original RNA sequence and the associated barcode and UMI are determined. Key to measuring abundance of each RNA and correctly associating them with their cell of origin is accurate assignment of the UMIs and barcodes.

Long-read sequencing approaches, such as those of Oxford Nanopore Technologies, are currently revolutionising bulk sequencing approaches. “Long-read single-cell technology has the potential to interrogate not only RNA abundance, but also splice variants, structural variation and chimeric transcripts at the single-cell level. Collectively, the ability to determine these features accurately will improve diagnostics and biological understanding. However, Nanopore sequencing can be inaccurate, which hinders the critical steps of barcode and UMI assignment, making its application to single-cell sequencing challenging,” explains Dr Martin Philpott, first author of the paper and Director of the Next-Generation sequencing facility at the Botnar Research Centre.

To overcome these challenges, the team has developed a new approach called single-cell corrected long-read sequencing (scCOLOR-seq) that identifies and corrects errors in the barcode and UMI sequences, permitting standalone cDNA Nanopore sequencing of single cells. “Each mRNA molecule is tagged with a short sequence which identifies it within a certain droplet,” adds Dr Cribbs. “However, Nanopore long-read sequencing is too error prone to reliably sequence these tags, making it difficult to map the mRNA back to its specific cell. What we’ve been able to do is to develop a practical method for building redundancy into the tag, allowing inaccuracies within the sequencing to be pinpointed, and then correct them. The mRNA can then be linked back to an individual cell.”

The research was developed in collaboration with ATDBio, an Oxford/Southampton based company, created by Professor Tom Brown Sr at the Chemistry Department, University of Oxford. Dr Tom Brown Jnr, Chief Scientific Officer of ATDBio, says, “The new scCOLOR-seq method is the first of many innovations resulting from our collaboration with the Botnar Research Centre team. The collaboration has been one of our most interesting and successful, and we are pleased to see our work recognised in Nature Biotechnology. It’s a great example of how we at ATDBio can apply our expert knowledge of nucleic acid chemistry and complex oligonucleotide synthesis to difficult problems in biology and beyond, together with our corporate and academic partners”.

“This study demonstrates an incredible cross-disciplinary team effort to advance single-cell technologies and is the result of strategic investments into these technologies at our department,” adds Professor Udo Oppermann, Director of Laboratory Sciences at the Botnar Research Centre and co-senior author of the paper. “We will continue our collaborative efforts to develop innovative single-cell approaches and – as demonstrated in the paper- apply this to molecular analyses in primary and secondary bone and other haematological cancers. Our intention is to advance these technologies in personalised medicine approaches such as cancer diagnosis allowing rational clinical decision making.”

New method for cost-effective genome-wide DNA methylation analysis

Cytosine, one of the four DNA bases, can be chemically modified by the addition of a molecule known as a methyl group to form 5-methylcytosine. This “epigenetic” modification has long been known to regulate gene expression and plays a critical role in processes like embryonic development. Its levels and distribution are also distinct in different tissues and are significantly altered in cancers. Analysing methylation patterns of DNA shed into blood and other bodily fluids by tumours can thus reveal both the presence and the location of a cancerous growth.

In 2019, Dr Chunxiao Song (Ludwig Institute for Cancer Research, Oxford Branch, Nuffield Department of Medicine) and his team developed TET-assisted pyridine borane sequencing (TAPS) for mapping DNA methylation. The technology was spun out in 2020 to establish the biotechnology company Base Genomics, which was acquired for $410 million by Exact Sciences in October 2020. Compared to the previous gold standard for sequencing DNA methylation, TAPS is far more cost-effective and sensitive, and generates cleaner data to allow for additional genetic analysis.

Yet despite its advantages, TAPS still relies on whole-genome sequencing, which remains an expensive approach for detecting DNA methylation since just ~4% of all cytosines in the genome are methylated. Chunxiao and his team have now developed a new method that cuts costs further by sequencing only those regions of the genome that contain methylated cytosines.

Building on the TAPS method, postdocs Dr Jingfei Cheng and Dr Paulina Siejka-Zielińska made use of molecular scissors called endonucleases that recognise and cut specific DNA sites. During TAPS, methylated cytosines are chemically converted to an altered base called dihydrouracil (DHU). The researchers found an endonuclease called USER enzyme that specifically cuts at DHU. Because of the enzyme specificity, they knew that all the DNA fragments produced had methylation sites at the beginnings and ends. By then size-selecting the DNA to exclude the larger, uncut DNA, only the smaller, cut DNA fragments with methylation sites are sequenced, making this approach more cost-effective for studying DNA methylation at base-pair resolution.

The team has named the new technique endonuclease enrichment TAPS (eeTAPS), and details on the method can be found in their publication in Nucleic Acids Research.

Using Herpesvirus to fight cancer

The Seymour lab at the Department of Oncology, University of Oxford, has published a new paper investigating the use of oncolytic herpes virus-1 as a vector to augment immunotherapy in cancer

Oxford success at the early detection sandpit on pancreatic cancer

Pancreatic cancer is a devastating disease with low survival rates that have hardly improved in the last 40 years. These cancers are very challenging to treat, in part due to their frequently late diagnosis when the cancer is already advanced.

To address this need for earlier detection, Cancer Research UK, Pancreatic Cancer UK and the Engineering and Physical Sciences Research Council convened a 3-day virtual workshop in November 2020. Multidisciplinary teams worked together to generate innovative research ideas for detecting pancreatic cancer earlier. At the end of the workshop, the teams pitched their ideas to receive seed funding for feasibility testing from a Cancer Research UK Early Detection Innovation Award. Two successful teams involved Oxford researchers.

Team ReTHOMS: Real-time high-sensitivity optrode metabolic sensor for pancreatic cyst fluids

Team ‘ReTHOMS’ includes Oxford’s Professor Eric O’Neill (Department of Oncology) who is working with Dr Paolo Bertoncello (Swansea University), Dr David Chang (University of Glasgow) and Dr George Gordon (University of Nottingham). The team aims to develop a new sensor device to detect malignant transformation in people with pancreatic cysts, a condition that puts them at higher risk of pancreatic cancer.

Pancreatic cysts are fluid-filled sacs on or in the pancreas that are mostly benign. However, 2-3% are precancerous and can develop into pancreatic cancer. Cysts are often identified incidentally and are then monitored for malignant transformation using either clinical imaging or analysis of the cyst fluid for cancer biomarkers such as mucins. Despite this surveillance regime, early cancers are still being missed since these methods have limited sensitivity and specificity.

To improve the early detection of malignant cyst transformation, the team aims to develop real-time and highly sensitive detection of an expanded range of cancer biomarkers. In addition to mucin, raised cellular levels of the chemical hydrogen peroxide are associated with cancer. So-called optrode technology will be used to detect hydrogen peroxide and mucin in cyst fluid. Optrodes are optical sensor devices that detect light emitted as a result of an electrochemical reaction with the biomarkers being analysed.

During this short project, the team will build the optrode device for measuring hydrogen peroxide and mucin, and undertake technical and biological validation. The longer-term aim of this research is to detect pancreatic cancer earlier by screening pancreatic cyst fluid at the point-of-care and determining further action based on the risk of cancer.

Team EDPAN: Earlier detection of pancreatic cancer through personalised assessment of risk combined with non-invasive infrared spectroscopy

Oxford’s Dr Pui San Tan (Nuffield Department of Primary Care Health Sciences) will work as part of team EDPAN with Dr Pilar Acedo Nunez (University College London), Dr Aida Santaolalla (King’s College London), Dr Paul Brennan (University of Edinburgh), Dr Lucy Oldfield (University of Liverpool), Dr Andrew Kunzmann (Queen’s University Belfast) and Dr Mohammad Golbabaee (University of Bath). This team aims to identify individuals at higher risk of pancreatic cancer for further diagnostic screening.

One of the reasons that pancreatic cancer is often diagnosed late is that symptoms are non-specific and cannot discriminate those that require investigation for pancreatic cancer. Team EDPAN will develop an approach for personalised risk stratification to identify individuals at higher risk that would benefit from more in-depth screening for pancreatic cancer.

During the project, the team will make use of existing cohorts for pancreatic cancer (ADEPTS (UCL) and PanDIA (Liverpool)) and larger cohorts for epidemiology research (UK Biobank, AMORIS). They will combine clinical and demographic information with analysis of serum and urine samples using a technique called infrared spectroscopy. They will also evaluate changes in immune components. These approaches aim to identify individuals at high-risk of pancreatic cancer and investigate whether addition of infrared spectroscopy data and immune analysis improves the accuracy of the risk prediction model.

Further funding secured to hunt out cancer using innovative radiotherapy techniques

Professor Bart Cornelissen and Dr Tiffany Chan, from the Department of Oncology, have received an additional £408,338 award from the charity Prostate Cancer Research (PCR) to continue their innovative work to help a new type of radiotherapy, designed to hunt out cancer even after it has spread, to benefit even more men with prostate cancer. Prostate cancer is now the most commonly diagnosed cancer in the UK and their work could lead to more personalised treatment for those with prostate cancer.

Bart and Tiffany are working with a type of radionuclide therapy called 177Lu-PSMA. PSMA seeks out a protein found almost exclusively on prostate cancer cells, and by linking it to radioactive Lutetium (Lu), it can guide the radiotherapy directly inside tumour cells. ‘An advantage of 177Lu-PSMA is that we don’t need to know where all the cancer cells are before treatment, unlike in external beam radiotherapy’ explains Tiffany. ‘In theory, even if we just have a single cell that has split away from the main tumour, if it expresses PSMA, we should still be able to target it.’

Some Lu-PSMA treatments are already used in the UK, but on a private basis only and at the moment they are primarily used for pain relief. The Oxford researchers aim to combine Lu-PSMA with other therapies, and their initial results, from testing nearly 2,000 drugs, have led to the discovery of a group of drugs that may be able to help 177Lu-PSMA hunt out prostate cancer better and make it more effective for more patients. This discovery, which led to further funding from PCR for them to continue this exciting work, comes at an important time for radionuclide therapies. ‘There’s a very large Phase 3 clinical trial with Lu-PSMA and that seems to suggest that you actually get benefits in overall survival from this treatment’ explains Bart. ‘Rather than just being pain relief, we can now start to think of these as cures as well.’

“Speaking as a patient whose prostate cancer has been previously treated with radiotherapy and is likely to be so again in the future, I find this work to be a very welcome addition to the treatments available for the disease,’ said prostate cancer patient David Matheson. ‘It is heartening to see such progress with this treatment, and I look forward to it becoming more widespread in the future.’

During lockdown, the closure of their lab meant they had to find alternative ways to reach their goal. They found an innovative solution – reversing their original plans and developing new and efficient ways to analyse results in lockdown first, and then conducting the experiments when they could return to the lab. Tiffany developed a network analysis tool to enable them to predict which combinations might work. ‘I’m a Londoner, so I like to think of it like a tube map, where have all of our different tube stops, connected by different tube lines, with some lines being more efficient than others. The idea behind mapping the system in this way is that we can hopefully find the best line, or in this case, the best biological pathway, that is most likely to lead to synergism with Lu-PSMA,’ she said. PCR initially awarded £100,000 to Bart and Tiffany in 2019 to test up to 1,000 drugs in combination with 177Lu-PSMA. Despite the challenges brought on by the Covid-19 pandemic, the team surpassed their target and managed to test an incredible number of drugs.

Bart and Tiffany are hopeful that Lu-PSMA could become more widespread in the clinic but believe more research needs to be done. ‘Lu-PSMA is the new kid on the block, it’s a very new technology. I think there’s still a lack of understanding about how Lu-PSMA itself works, and there’s a lot of biology we can learn to improve its efficacy’ says Tiffany. ‘So that’s what we’re trying to achieve, particularly with our network analysis approach to map out the biology behind it.’

‘Bart and Tiffany’s project is already showing promising results on the route to improving radiotherapy for men with prostate cancer. We look forward to continuing to support their project on a larger and long-term basis and hope it will mean that more people can benefit from enhanced radiotherapy, without the side effects’

– Dr Naomi Elster, Head of Research and Communications, PCR

‘There are Lu-PSMA treatments that are already given in the UK but on a private basis’ Bart explains. ‘Whether that will hit the NHS depends on approval by NICE but given the fantastically positive data out there, the upcoming results of the VISION Phase 3 clinical trials that are very positive, and given the improvement in actual survival of patients, I think there is good hope there that that will be approved.’

– Professor Bart Cornelissen

“Perhaps, what is most exciting is that, by targeting PSMA, this therapy delivers the radiotherapy directly to the sites of the cancer, wherever they are located. It is heartening to see such progress with this treatment, and I look forward to it becoming more widespread in the future.”

– David Matheson, prostate cancer patient

For more information, please visit: www.pcr.org.uk. Full story on the Department of Oncology website.

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.

Oxford spin out influencing patient care world wide

Optellum, a lung health company aiming to redefine early diagnosis and treatment of lung disease, today announced it received FDA clearance for its “Virtual Nodule Clinic”.

Optellum was co-founded by Oxford cancer researcher Prof. Sir Michael Brady with the mission of seeing every lung disease patient diagnosed and treated at the earliest possible stage, and cured.

Optellum’s initial product is the Virtual Nodule Clinic, the first AI-powered Clinical Decision Support software for lung cancer management. Their platform helps clinicians identify and track at-risk patients and speed up decisions for those with cancer while reducing unnecessary procedures.

Lung cancer kills more people than any other cancer. The current five-year survival rate is an abysmal 20%, primarily due to the majority of patients being diagnosed after symptoms have appeared and the disease has progressed to an advanced stage. This much-needed platform is the first such application of AI decision support for early lung cancer diagnosis cleared by the FDA.

Physician use of Virtual Nodule Clinic is shown to improve diagnostic accuracy and clinical decision-making. A clinical study, which underpinned the FDA clearance for the Virtual Nodule Clinic, engaged pulmonologists and radiologists to assess the accuracy for diagnosing lung nodules when using the Optellum software.

Dr Václav Potěšil, co-founder and CEO of Optellum says:

“This clearance will ensure clinicians have the clinical decision support they need to diagnose and treat lung cancer at the earliest possible stage, harnessing the power of physicians and AI working together – to the benefit of patients.

Our goal at Optellum is to redefine early diagnosis and treatment of lung cancer, and this FDA clearance is the first step on that journey. We look forward to empowering clinicians in every hospital, from our current customers at academic medical centers to local community hospitals, to offer patients with lung cancer and other deadly lung diseases the most optimal diagnosis and treatment.”

New partnership enables access to state-of-the-art radiotherapy machine

The first NHS patient has received treatment on the cutting-edge ViewRay MRIdian technology, thanks to a new partnership between the University of Oxford, Oxford University Hospitals (OUH) NHS Foundation Trust and GenesisCare.

The partners, with the support of the John Black Charitable Foundation, have collaborated to establish a ten-year programme of clinical treatment for NHS patients, with further research into improving cancer treatment using the Viewray MRIdian.

Due to the natural, unavoidable movement of soft tissue inside the body, normal tissue around the cancer can be exposed to radiotherapy treatment, particularly when targeting soft-tissue tumours deep within the body. It can be challenging to visualise these organs during radiotherapy with routine radiotherapy delivery.

The ViewRay MRIdian machine is the only one of its kind in the UK, with only 41 machines worldwide. It allows doctors to see the normal soft tissue and the tumour in real time by combining MRI scanning with targeted radiotherapy. Incorporating MRI scans will allow doctors to then tailor doses in real time to the specific internal anatomy of the patient on the day of treatment.

MRIdian technology also minimises the damage to surrounding healthy tissues by switching off when tumour tissue moves outside of the targeted beam. This could mean less side effects for patients and increased dosage of treatment delivered directly to the tumour.

GenesisCare, the University of Oxford and OUH will also partner in research collaborations to develop real-world evidence which will inform future utilisation of the MRIdian technology in hard-to-reach tumours, such as pancreatic cancers. The research partnership will assess the benefits of the MRIdian technology in terms of improved cancer outcomes and reduced toxicity.

Elizabeth Rapple, from South Oxfordshire, is the first patient to use the machine to treat her renal cancer, as part of the new partnership. She says:

“I feel very fortunate to be able to access this machine as part of a new Oxford-wide partnership. Any operation to remove my tumour would have been highly invasive, so it’s lucky that my cancer was suitable for MRIdian radiotherapy. I am so grateful that this unique machine has been made accessible through the NHS, and that I can be the first of many to benefit from this partnership going forward.”

Project leader Professor Tim Maughan, from the University of Oxford, said:

“Treating patients on the MRIdian is like a surgeon putting on their spectacles for an operation – for the first time we can see exactly what the cancer is doing during treatment and adapt to change accordingly.  This accuracy allows us to reduce side effects and we hope to improve cancer outcomes in hard-to-treat cancers.”

Dr James Good, Clinical Oncologist at GenesisCare, said:

“The MRIdian machine is at the cutting-edge of what is possible in radiotherapy technology. The ability to visualise the tumour more accurately, to follow it while it’s being treated and to adapt the plan every day means we can deliver the best possible outcomes.

“This collaboration with the University of Oxford and Oxford University Hospitals will be truly beneficial for cancer patients in the UK. Not only will it provide patients who otherwise would have limited, or sadly, no options with a really viable treatment option, but we can also help demonstrate the effectiveness of this treatment, with the ambition to make it available for all NHS patients in the future.”

Carol Scott, Lead Therapeutic Radiographer & Deputy Clinical Director at Oxford University Hospitals , said:

“OUH are excited to be part of this collaboration offering NHS patients the opportunity to take part in these clinical trials. The use of daily advanced imaging that clearly shows us the tumour and normal soft tissue around it will enable us to take the next step in making our treatments even more personalised and effective”

Developing a system to simultaneously detect genetic and epigenetic information

Many diseases are associated with changes to the DNA sequence, most notably cancer. Also altered in disease is the way that the DNA is decorated with chemical modifications such as methylation (epigenetic modifications). Being able to extract genetic and epigenetic information using DNA sequencing has revolutionised biomedical research and has led to new ways to diagnose diseases. A particular interest currently is in using genetic and epigenetic characteristics of tumour DNA circulating in the blood or other bodily fluids as a strategy for detecting cancer earlier. However, despite the potential utility of combining genetic and epigenetic information to enhance disease detection, no methods currently exist that can efficiently simultaneously extract this information from the same DNA sequencing data.

Up until now, DNA methylation has predominantly been detected using methods that rely on a process called bisulphite conversion. Bisulphite is a harsh chemical that damages DNA, resulting in decreased sensitivity and a high error rate in the sequencing data. Because it is not known whether any changes in the DNA compared to a reference genome are introduced by bisulphite or real mutations, it is very challenging to simultaneously detect methylation and mutation data using these methods.

Recently, a new bisulphite-free method for detecting DNA methylation called TET-assisted pyridine borane sequencing (TAPS) has been developed by Ludwig Oxford’s Dr Chunxiao Song and Dr Benjamin Schuster-Böckler. This method is both cheaper than bisulphite sequencing and importantly produces data of higher quality, similar to that of standard DNA sequencing.

In this project, funded by an MRC Methodology Research Grant, Dr Benjamin Schuster-Böckler will collaborate with Professor Gerton Lunter (Visiting Professor, Radcliffe Department of Medicine) to develop algorithms that simultaneously detect mutations and DNA methylation from TAPS data.  Experimental data will be provided in collaboration with Ludwig Oxford’s Dr Chunxiao Song and Professor Xin Lu, and Professor Ellie Barnes (Nuffield Department of Medicine). Test data will be used to train machine-learning algorithms to optimise the accuracy of the sequencing method and to establish the best possible experimental parameters for this technique.

The resulting method will greatly increase the utility of the TAPS technique and will make it possible to routinely query a patient’s genetic background, while simultaneously measuring their epigenetic state. This will lead to a much broader understanding of the role of epigenetics in disease and would raise the possibility of using combined genetic and epigenetic information from sequencing data to aid earlier detection of cancer.

Image attribution: Darryl Leja, National Human Genome Research Institute (NHGRI) from Bethesda, MD, USA, CC BY 2.0 https://creativecommons.org/licenses/by/2.0, via Wikimedia Commons

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.”