The publication of a new report marking progress under Wales’ first national cancer research strategy offers a timely opportunity to reflect on how immunology is reshaping cancer research across the nation. Led by the Wales Cancer Research Centre,1 who are funded by Welsh Government through Health and Care Research Wales,2 the Cancer Research Strategy (CReSt)3 was backed by a £1m implementation award to support the delivery of the strategy across Wales. The new CReSt report4 is both a stocktake of achievements since 2022 and a forward-looking statement of intent – one that underscores the growing role of immunology in shaping future research.
Immunology takes centre stage
Immuno-oncology has advanced significantly over the past two decades, alongside a clearer understanding of how tumours avoid immune detection. As Professor Awen Gallimore (Division of Infection and Immunity, Cardiff University) has observed, cancers employ ‘barriers and disguises’ that limit immune recognition – mechanisms that are now being systematically investigated and, in some cases, overcome.
The CReSt report4 highlights how researchers in Wales are addressing these challenges by examining tumour–immune interactions at multiple levels. Importantly, this work is embedded in translation and clinical application. A key feature of the Welsh research environment is its emphasis on translation, with immunological insights increasingly informing early-phase studies and patient-focused research.
T cells on the attack
Researchers at Cardiff University are developing new ways to harness T cells to improve immunotherapy and cancer vaccines. Across multiple programmes spanning discovery science translational immunology and clinical studies, the work is helping position Wales at the forefront of next-generation cancer immunotherapy.
Professors Andrew Godkin and Awen Gallimore recently secured a Cancer Research UK Discovery Programme grant to investigate how CD4+ T cells can be better mobilised against cancer. Although many immunotherapies have historically focused on CD8+ ‘killer’ T cells, there is growing recognition that CD4+ T cells play a central coordinating role in generating durable antitumour immunity.
Supported by the Bowelbabe Fund for Cancer Research UK, the Cardiff team is now working towards a universal bowel cancer vaccine (Figure 1). Working with structural immunologist, Dr Bruce MacLachlan (Figure 2 and 3), the researchers are identifying tumour antigens shared across many bowel cancers and modifying them to improve immune recognition. The goal is to develop more accessible ‘off-the-shelf’ vaccines capable of stimulating robust anticancer immune responses across broad patient groups.
Alongside vaccine development, Professor Godkin is Chief Investigator of a Cancer Research Wales-funded 500-patient colorectal cancer study examining whether modulation of regulatory T cells can enhance antitumour immunity. Together, these programmes aim not only to improve treatment for established cancers but potentially to develop preventative immune strategies for high-risk patients.
Professor Godkin said: “Our research is focused on helping the body’s immune system better recognise cancer. We do this by slightly changing certain proteins made by cancer cells to make them more visible to the immune system.”
Researchers at Cardiff are also investigating more fundamental questions about how the immune system naturally controls cancer. Professor Andrew Sewell and Dr Garry Dolton study exceptional cancer survivors whose immune systems appear to have eliminated advanced cancers. By analysing these rare cases, the group hopes to uncover entirely new mechanisms of cancer recognition.
Recent work published in Cell demonstrated how human T cells can exploit previously unrecognised vulnerabilities shared across multiple cancers. The team has also identified unconventional T-cell responses capable of recognising cancers independently of classical HLA-restricted mechanisms, challenging long-standing assumptions in tumour immunology.
One particularly important area has been research into MR-restricted T cells. Unlike conventional T cells, which recognise cancer through highly variable HLA molecules, MR-restricted T cells target the highly conserved MR1 molecule, raising the possibility of therapies applicable across many patients. Cardiff researchers have helped show that these responses can arise naturally in humans, retain selectivity for cancer cells over healthy tissue, and may involve shared T-cell receptor features across different individuals. The group has also developed new MR1-based tools capable of identifying these rare anticancer T cells directly.
The programme combines discovery science with clear translational ambition. The Sewell team is part of the international NexTGen Grand Challenge consortium, funded by Cancer Research UK, the US National Cancer Institute and The Mark Foundation for Cancer Research, which aims to develop next-generation engineered T-cell therapies for children with solid cancers.
Meanwhile, Professor Gallimore’s laboratory is investigating why many cancer-specific T cells fail to penetrate solid tumours effectively. Supported by Cancer Research UK programme funding, the group has shown that activated T cells can remodel tumour blood vessels in ways that facilitate further immune-cell infiltration and tumour destruction (Figure 4). Working with medical oncologist, Dr Paul Shaw, and imaging scientist, Dr Marco Palombo, through the Wales Cancer Research Centre, the team is now investigating whether similar vascular changes occur in patients receiving immunotherapy.
Using viruses to kill cancer
Another major research theme emerging from Cardiff is oncolytic virotherapy, i.e. the use of engineered viruses to attack cancer cells while simultaneously activating the immune system.
Led by Professor Alan Parker, Head of Solid Cancers at Cardiff University, researchers are developing viruses that selectively infect tumours while sparing healthy tissue. The programme has now progressed into clinical testing through the ATTEST Phase 1 trial, which is evaluating a novel virus-based therapy called TROCEPT-01 (ATTR-01) in patients with advanced solid tumours.
Originally developed in Professor Parker’s laboratory and licensed to Accession Therapeutics Ltd in 2021, TROCEPT-01 uses a genetically engineered virus that replicates selectively within cancer cells. As the virus spreads through the tumour, it destroys cancer cells directly while also delivering a gene that enables tumours to produce a checkpoint inhibitor locally.
The strategy effectively turns tumours into local ‘factories’ for immunotherapy while limiting systemic exposure. The programme recently received €7.5 million in Horizon Europe funding to support further clinical development and expansion of the trial internationally.
The ATTEST trial is led by Professor Adel Samson at Leeds University Hospitals NHS Trust. In Wales, the study is delivered through collaboration between Velindre University NHS Trust and Cardiff and Vale University Health Board, supported by the Cardiff Cancer Research Partnership.
Professor Parker said: “TROCEPT-01 has been designed to have minimal activity in healthy tissues, with maximal activity in the tumour. This potent and highly localised activity gives promise in many cancers of unmet clinical need.”
Cardiff researchers are also exploring how viruses can redirect pre-existing antiviral immunity against cancer. Supported by the Wales cancer Research Centre, an Academy of Medical Sciences Springboard Award and ARC Academy funding, Dr Carly Bliss, Group Leader in Cancer Immunology at Cardiff University, is developing tumour-targeting viruses that deliver highly immunogenic viral epitopes directly into cancer cells. Rather than relying solely on tumour-associated antigens, the strategy aims to harness strong antiviral immune responses already present within the population and redirect them towards solid tumours.
Brain
Cardiff University is also developing significant expertise in brain cancer research with early career researchers playing a major role in advancing the field. Embedded within the research community are two Brain Tumour Charity Future Leader Fellows, Dr Mathew Clement and Dr Emily Bates, who are researching glioblastoma (GBM), the most aggressive and common form of brain cancer, where survival remains extremely poor.
Dr Clement, with additional support from Cancer Research Wales, an Academy of Medical Sciences Springboard award and the Rosetrees Trust, is developing nanoparticle and bispecific reagents that can cross the restrictive blood–brain barrier and are capable of remodelling the T-cell response within the tumour, with early preclinical studies showing encouraging results (Figure 5). He has also developed a toolkit to interrogate antigen-specific T-cell responses within GBM.
Dr Bates’ work focuses on engineering viruses capable of delivering immunotherapies directly into brain tumours while stimulating anticancer immune responses within the tumour microenvironment. Additional funding through UKRI Proof of Concept and MRC Impact Acceleration Awards is enabling the testing of these therapies in clinically relevant glioblastoma models.
Future plans
As the CReSt strategy moves into its next phase, priorities include expanding successful programmes and strengthening collaborative links across discovery and clinical research. The CReSt report4 points to continued growth in areas such as vaccine development and early-phase trials. Professor Richard Adams, National Clinical Research Lead for the Tackling Cancer Through Research, said: “This report demonstrates the real momentum we are building in cancer research across Wales. From breakthrough scientific discoveries to large-scale clinical trials, we are seeing Welsh-led research that has the potential to change outcomes for patients.”
For immunology, the Welsh model highlights the value of linking mechanistic research with strong clinical infrastructure, allowing discoveries made in the laboratory to be explored rapidly in patient settings. Across Wales, researchers are combining expertise in T-cell biology, tumour immunology, virology, microbiome science and early-phase clinical trials to tackle some of the biggest remaining challenges in cancer treatment.
The next phase of the CReSt strategy will focus not only on improving existing immunotherapies, but also on discovering entirely new ways in which the immune system can recognise and control cancer. By combining fundamental discovery science with translational ambition, researchers in Wales aim to accelerate the development of more effective, broadly accessible immune-based treatments for cancer.
Links to labs:
https://ccrp.org.uk/immuno-oncology-and-advanced-therapies/
https://www.cancerimmunology.co.uk/
https://www.cardiff.ac.uk/wales-applied-virology-unit
References
- Wales Cancer Research Centre http://walescancerresearchcentre.org/
- Health and Care Research Wales https://healthandcareresearchwales.org/
- Cancer Research Strategy (CReSt) https://walescancerresearchcentre.org/crest/
- CReSt report https://walescancerresearchcentre.org/wp-content/uploads/ENG_CReSt2026.pdf