Scientists at the University of Southampton’s Centre for Cancer Immunology have 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 humans in clinical trials, this has been less successful, and although it is safe for the patient, they have not caused strong anti-tumour responses.
In the new study, published in the Journal for ImmunoTherapy of Cancer, the team showed the antibody (hIgG1 isotype) they used in the patients is the most effective type of antibody in the pre-clinical research and that it can act both by killing suppressive T cells called Tregs, as well as activating the killer T cells, to boost the immune anti-cancer response. 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.”