Scientists are utilising the same technology used in the creation of the Oxford-AstraZeneca COVID-19 jab to develop a vaccine to treat cancer.
Researchers at the University of Oxford and the Ludwig Institute for Cancer Research have designed a two-dose therapeutic cancer vaccine using Oxford’s viral vector vaccine technology. The cancer vaccine, which has already been tested in mouse tumour models, has been shown to increase the levels of anti-tumour T cells infiltrating the tumours and improve the efficacy of cancer immunotherapy.
The study has been published in the Journal for ImmunoTherapy of Cancer.
Immunotherapy
The process of cancer immunotherapy involves turning a patient’s own immune system against a tumour. PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of ‘off switch’ that helps to prevent the T cells from attacking other cells in the body. Anti-PD-1 immunotherapy works by taking the brakes off these anti-tumour T cells, enabling them to kill cancer cells. Although this therapy has proved hugely successful in some cancer patients, it is ineffective for most.
Researchers have sighted low levels of anti-tumour T cells in some patients as one of the reasons for the poor efficacy of anti-PD-1 cancer therapy. The vaccine technology behind the Oxford-AstraZeneca COVID-19 vaccine generates strong CD8+ T cell responses, which are required for good anti-tumour effects.
In this study, the researchers 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. To create a vaccine that specifically targets cancer cells, it was designed to target two MAGE-type proteins that are present on the surface of many types of cancer cells. Known as MAGE-A3 and NY-ESO-1, these two targets were previously validated by the Ludwig Institute.
Reduction in tumour size
When trialled in preclinical experiments using mouse tumour models, the 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, said: “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.”
In the next step of this research, scientists will carry out 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. This trial is due to take place 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, said: “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, said: “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.”
