Group Leader, Adán Pinto-Fernández, has won a competitive Oxford Cancer Immuno-Oncology Network (OCION) Pump Priming Award to fund his research project 'Targeting ISGylation to Boost Cancer Antigenicity: A Novel Approach for Cancer Immunotherapy'. The mission of the OCION Funding Scheme is to provide short-term awards that pump-prime innovative, high-risk and proof-of-concept Oxford-based immuno-oncology research. The project was awarded following a review of all the application by OCION's scientific and patient and public involvement committee.
Following the award, Adán had a conversation with OCION about his research and how the award will support his group:
Tell us about yourself and where you work.
My name is Adán Pinto-Fernández, and I am a Career Development Fellow and Junior Group Leader in cancer research and therapeutics, with over 20 years of experience. Throughout my career, I’ve explored diverse areas within cancer research, including oncogenic Ras biology at the Universidad de Cantabria in Spain, the pharmacology of the tumour microenvironment at Université Catholique de Louvain in Belgium, and cancer inflammation and therapeutics at the University of Oxford.
In November 2021, I established my research lab with the support of a CAMS Oxford Institute Career Development Award. We are based at the CAMS Oxford Institute, located on the Old Road Campus in Oxford, as part of the Nuffield Department of Medicine.
Tell us a little about your research.
Our research focuses on reactivating the body’s natural defences that cancer cells often switch off to evade the immune system. Normally, cells use a process called type I Interferon (IFN-I) signalling to defend against viruses and other threats. Cancer cells, however, can shut down this defence, allowing them to ‘hide’ from the immune system.
With support from the OCION funding scheme, we are exploring a specific process called ISGylation, where a protein called ISG15 tags other proteins inside the cell upon excessive IFN-I signalling activation. This tagging could make cancer cells more recognisable to the immune system by increasing the number of antigens - or unique markers - on their surface.
Notably, our collaborator Prof. Vincenzo D’Angiolella’s lab in Edinburgh has shown that when glioblastoma cells (a type of brain cancer) are exposed to radiation, they also accumulate proteins tagged with ISG15. This finding provides an excellent model to study how ISGylation regulates cancer cell visibility. Thanks to the OCION funding, we will have access to a specialised technique called immunopeptidomics, mastered by our collaborator Dr. Eleni Adamopoulou. This technique allows us to identify and measure these ‘tags’ in detail, helping us understand how ISGylation might make cancer cells more visible to the immune system. Ultimately, this research could pave the way for new approaches that empower the immune system to better recognise and fight cancer.
What are the potential implications of this work for patients?
Our research has promising potential to improve cancer treatment. By understanding how ISGylation increases the amount and diversity of cancer antigens on the cell surface - including unique cancer markers called neoantigens - we aim to explore new ways to enhance how the immune system recognises and targets cancer cells. This knowledge could open up new avenues for patient-centred therapies, such as cancer vaccines, adoptive cell therapies, antibody-based treatments, and even improve responses in patients undergoing immune checkpoint blockade therapies.
What do you think are the major obstacles for the cancer field to overcome in the next 10 years?
In my view, while cancer research has made great strides in saving lives, the field still faces two significant challenges in the coming decade:
- Understanding Cancer Initiation for Early Detection: We need to deepen our understanding of how cancer begins, which would allow us to detect it and initiate treatment at its earliest stages - ideally before it has grown or spread to a point where it becomes difficult to treat.
- Advancing Personalised Medicine: Cancer therapies currently face challenges, as they don’t work equally well for everyone, and resistance mechanisms or severe side effects can develop unpredictably. Further research into personalised medicine is essential to create tailored therapies that are effective and safe for diverse patient populations.
Constantly evolving technological advancements will help us tackle these challenges head-on, expanding our understanding of cancer and bringing us closer to a cure.
What does Oxford Cancer and OCION mean for you and your research?
Oxford Cancer and OCION represent invaluable hubs of collaboration for our research. Over the years, we have had the opportunity to work with many centre members, bringing together basic scientists, technologists, patients, and clinicians. This unique combination of expertise and perspectives has significantly advanced our research, allowing us to address critical unmet needs in cancer treatment.
Receiving an OCION funding award is both a privilege and a powerful opportunity to deepen our engagement with this collaborative community. It allows us to contribute further to the shared goal of improving patient lives and bringing innovative immune-based solutions to cancer care.