A groundbreaking study has demonstrated how bacteria-killing viruses, known as phages, can be genetically engineered to harness pre-existing vaccine immunity and destroy cancer cells. In experiments conducted on mice, this novel approach successfully eradicated tumours in nearly half of the treated animals, offering a potential new direction for cancer immunotherapy.
Immunotherapy, which leverages the body's own immune system to combat cancer, has revolutionised treatment for certain forms of the disease. However, a significant challenge remains in enabling the immune system to effectively recognise and target cancerous cells. Researchers at Imperial College London, led by Amin Hajitou, sought to overcome this by focusing on a specific phage that typically infects E. coli bacteria.
The team genetically modified this phage to bind to proteins called αvβ3 and αvβ5 integrins, which are found in abundance on many tumour cells but are largely absent from healthy tissue. Crucially, they also engineered the phage to deliver instructions for producing a malaria-specific antigen – a molecular signal that the immune system, once primed by a malaria vaccine, would recognise as foreign. This effectively turns the phage into a targeted delivery vehicle, guiding the immune response directly to the cancer cells.
In tests involving 60 mice with subcutaneous cancerous tumours, 15 received a malaria vaccine followed by six injections of the engineered phages over two weeks. The results were compelling: 44 per cent of these treated mice saw their tumours completely eradicated, with no recurrence observed a year later when the study concluded. Other treated mice also exhibited increased survival rates compared to control groups that received no intervention, only the vaccine, or only the phages.
According to David Withers at the University of Oxford, a key advantage of this method is the ability to administer these modified viruses systemically, allowing them to locate and infect tumour cells throughout the body. This significantly improves upon current approaches like oncolytic viruses, which often require direct injection into the tumour, limiting their use in cases of metastatic disease where cancer has spread.
The researchers believe that by adjusting the phage's antigen-making instructions, this approach could be adapted to work with immunity from other common vaccines, such as those for seasonal flu or Covid-19. This flexibility could broaden its applicability across a wider patient population. Discussions are now underway with the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK to assess the feasibility of an early-stage human trial, with hopes of commencing next year.