Scientists at the Centre for Cancer Immunology recently gained new insight into how the immune system can be better used to find and kill cancer cells.
The team, led by Dr Jane Willoughby and Professor Mark Cragg, in collaboration with GSK, have been studying OX40, a ‘co-receptor’ that helps to stimulate the production of helper and killer T-cells during an immune response.
In pre-clinical research, antibodies that bind OX40 have been shown to create impressive anti-tumour effects, causing the tumours to shrink and disappear.
However, in clinical trials with humans, this has been less successful, and although it is safe for the patient, the antibodies have not caused strong anti-tumour responses.
In the new study, published in the Journal for ImmunoTherapy of Cancer, the team showed that the antibody they used in clinical trial participants is the most effective type from the pre-clinical research. This antibody, called hIgG1 isotype, can act in two ways to boost the immune anti-cancer response: firstly, by killing suppressive T cells, called Tregs, and secondly by activating the killer T cells. However, the extent of how effective it is, depends on the type of tumour.
Professor Mark Cragg said: “Clinical trials with anti-OX40 antibodies have shown that the body can tolerate these drugs but unfortunately have also shown disappointing clinical responses. We need to understand why this is. Based on these results, we propose that OX40 antibodies may need to be more selectively matched to appropriate human tumours where their killing mechanisms can work more effectively for the patient.”
Although the clinical response was disappointing, it provided Professor Cragg and his colleagues with more information about anti-OX40 antibodies. Their research going forward will focus on a more selective approach to find the best treatment for patients.