- Research from the University of Oxford and the Ludwig Institute for Cancer Research has shown that the technology behind the Oxford-AstraZeneca COVID-19 vaccine has potential in treating cancer.
- A new publication has shown that a viral vector cancer vaccine generates effective anti-tumour immune responses and, in combination with immunotherapy, decreases tumour size and increases survival rates in mouse models.
- A first-in-human clinical trial of the therapeutic cancer vaccine in patients with non-small cell lung cancer will commence later this year.
Scientists from the University of Oxford and the Ludwig Institute for Cancer Research are building on the success of the Oxford-AstraZeneca vaccine against SARS-CoV-2 to develop a vaccine to treat cancer. Researchers have designed a two-dose therapeutic cancer vaccine using Oxford’s viral vector vaccine technology. When tested in mouse tumour models, the cancer vaccine increased the levels of anti-tumour T cells infiltrating the tumours and improved the efficacy of cancer immunotherapy. Compared to immunotherapy alone, the combination with the vaccine showed a greater reduction in tumour size and improved the survival of the mice.
The study, which was done by Professor Benoit Van den Eynde’s group at the Ludwig Institute for Cancer Research, University of Oxford in collaboration with co-authors Professor Adrian Hill and Dr Irina Redchenko at the University’s Jenner Institute, has today been published in the Journal for ImmunoTherapy of Cancer.
Cancer immunotherapy - turning a patient’s own immune system against a tumour – has resulted in remarkable improvements in outcomes for some cancer patients. Anti-PD-1 immunotherapy works by taking the brakes off anti-tumour T cells to allow them to kill cancer cells. However, despite this success, anti-PD-1 therapy is ineffective in the majority of cancer patients.
One reason for the poor efficacy of anti-PD-1 cancer therapy is that some patients have low levels of anti-tumour T cells. Oxford’s vaccine technology, used in the creation of the world-famous Oxford-AstraZeneca COVID-19 vaccine, generates strong CD8+ T cell responses, which are required for good anti-tumour effects.
The team developed a two-dose therapeutic cancer vaccine with different prime and boost viral vectors, one of which is the same as the vector in the Oxford-AstraZeneca COVID-19 vaccine. In order to create a vaccine treatment that specifically targets cancer cells, the vaccine was designed to target two MAGE-type proteins that are present on the surface of many types of cancer cells. Called MAGE-A3 and NY-ESO-1, these two targets were previously validated by the Ludwig Institute.
Preclinical experiments in mouse tumour models demonstrated that the cancer vaccine increased the levels of tumour-infiltrating CD8+ T cells and enhanced the response to anti-PD-1 immunotherapy. The combined vaccine and anti-PD-1 treatment resulted in a greater reduction in tumour size and improved the survival of the mice compared to anti-PD-1 therapy alone.
Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford, Member of the Ludwig Institute for Cancer Research and Director of the de Duve Institute, Belgium, says: ‘We knew from our previous research that MAGE-type proteins act like red flags on the surface of cancer cells to attract immune cells that destroy tumours.
‘MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumour types. This broadens the potential benefit of this approach to people with many different types of cancer.
‘Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side-effects caused by the immune system attacking healthy cells.’
A Phase 1/2a clinical trial of the cancer vaccine in combination with anti-PD-1 immunotherapy in 80 patients with non-small cell lung cancer will be launched later this year as a collaboration between Vaccitech Oncology Limited (VOLT) and Cancer Research UK’s Centre for Drug Development.
Adrian Hill, Lakshmi Mittal and Family Professorship of Vaccinology and Director of the Jenner Institute, University of Oxford, says: ‘This new vaccine platform has the potential to revolutionise cancer treatment. The forthcoming trial in non-small cell lung cancer follows a Phase 2a trial of a similar cancer vaccine in prostate cancer undertaken by the University of Oxford that is showing promising results.
‘Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumours and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer.’
Tim Elliott, Kidani Professor of Immuno-oncology at the University of Oxford and co-Director of Oxford Cancer, says: ‘In Oxford, we are combining our fundamental scientific expertise in immunology and antigen discovery with translational research on vaccine platforms.
‘By bringing these teams together we can continue to address the significant challenge of broadening the positive impact of immunotherapy to benefit more patients.’
This vaccination approach using different prime and boost viral vectors was licensed by Jenner Institute scientists to Vaccitech Ltd, founded in 2016. The new therapeutic cancer vaccine is being developed by Vaccitech Oncology Limited (VOLT), a strategic collaboration between the Ludwig Institute for Cancer Research and Vaccitech Plc.
Notes to editors:
For more information, including interview requests, contact Gen Juillet, Media Relations Manager, University of Oxford, firstname.lastname@example.org
This new paper, ‘Heterologous prime-boost vaccination targeting MAGE-type antigens promotes tumor T-cell infiltration and improves checkpoint blockade therapy’ is published on Friday 3rd September 2021 in the Journal for ImmunoTherapy of Cancer at http://dx.doi.org/10.1136/jitc-2021-003218
This study was co-led by Professor Benoit Van den Eynde and Dr Carol Leung at the Ludwig Institute for Cancer Research, University of Oxford. It was funded by the Ludwig Institute for Cancer Research, and the Cancer Research UK Oxford Centre.
About the University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the fifth year running, and at the heart of this success is our ground-breaking research and innovation. Oxford is world-famous for research excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research sparks imaginative and inventive insights and solutions.
Oxford University’s cancer research is managed through Oxford Cancer: a city-wide network and partnership between Oxford University and Oxford University Hospitals NHS Trust based on the University’s Translational Biomedical Research Campus.
With over 900 cancer research scientists spread across the city and beyond, Oxford is ideally placed to enable and combine the best research and clinical resources in order to innovate cancer treatment and care world-wide.
About Ludwig Cancer Research
Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for 50 years. Ludwig combines basic science with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Since 1971, Ludwig has invested nearly $3 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit www.ludwigcancerresearch.org.