By Holly Giles
Cardiff’s research has been the focus of international news this month through a breakthrough in cancer research. Professor Andrew Sewell has been leading the research at Cardiff University’s School of Medicine where they may have found a new treatment suitable for all cancers; he explained the work “raises the prospect of a one-size-fits-all cancer treatment”.
A widely used therapy known as CAR-T has been built upon in this research. The method uses the body’s own T cells, which are part of the immune system, and builds upon existing therapies. Currently it involves blood being taken from a cancer patient, the T-cells being separated from the blood and modified. Here they add genes for a cancer receptor known as CAR. These cells are then grown and inserted back into the patient so that they can detect cancer cells and destroy them. So far this theory has proved better on paper than in practice as it is only able to work on a few types of cancers and cannot work on solid tumours which make up most cancers. However, this limitation could be changed by the new research.
The new method:
The finding by Cardiff University, is a new type of T cell which has a different T-cell receptor that is able to recognise and kill most human cancers whilst ignoring healthy cells. This receptor, called MR1, is able to scan cells and recognise if they are cancerous due to a molecule present on the cell’s surface called human leukocyte antigen (HLA). Many different types of cancer have all shown to have this same HLA and it does not vary from person to person. This means not only could the new T cells be used on all types of cancer in a patient but also for other patients as it may not need to be patient specific. This has previously been a limitation of HLAs as they vary so much from person to person but MR1 has been seen to be the same across the population so overcomes this hurdle.
This new T-cell was reportedly found by accident as researchers were analysing blood from a bank in Wales looking for immune cells that could fight bacteria, when they found the new cell.
Andrew Sewell explained the work in his statement; “We hope this new T-cell receptor (TCR) may provide us with a different route to target and destroy a wide range of cancers in all individuals. Current TCR-based therapies can only be used in a minority of patients with a minority of cancers. Cancer-targeting via MR1-restricted T-cells is an exciting new frontier – it raises the prospect of a one-size-fits-all cancer treatment; a single type of T-cell that could be capable of destroying many different types of cancers across the population. Previously nobody believed this could be possible.”
So far, when T cells were given the new receptor they have been able to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells while ignoring healthy cells. They have also used human tissue from melanoma patients and shown that the receptor can kill cancerous cells of the patient and other patients’ cancer cells, suggesting as theorised that this new treatment may not need to be individual. This has currently only been done in a laboratory setting with isolated organs but researchers are now moving on to animal models.
The team have also tested this ability in living subjects through the use of mice with induced human cancers and an immune system similar to humans. The T-cells have been injected and the results have been observed; the researchers described an “encouraging rate of cancer clearing” that is higher than the current rates with T-cell therapy.
Professor Awen Gallimor of Cardiff University’s division of infection and immunity said; “If this transformative new finding holds up, it will lay the foundation for a universal T-cell medicine, mitigating against the tremendous costs associated with the identification, generation and manufacture of personalised T-cells. This is a truly exciting and potentially a great step forward for the accessibility of cancer immunotherapy.”
It’s still early stages for the research and as Daniel Davis from the University of Manchester explained; “At the moment, this is very basic research and not close to actual medicines for patients. There is no question that it’s a very exciting discovery, both for advancing our basic knowledge about the immune system and for the possibility of future new medicines.” However, these medicines may not be too far off with human trials expected to start by the end of the year according to the team.
The research is definitely not over for the team as they now hope to understand the mechanism by which the new TCR selects cancerous cells. They are hypothesised this could be through sensing changes in the metabolism of the cell, resulting in different compounds being present on the surface but it’s currently only a theory. They hope to solve this question and then look into its possibility of working on humans will the goal of human trials starting before the end of 2020. Professor Sewell explained; “There are plenty of hurdles to overcome however if this testing is successful, then I would hope this new treatment could be in use in patients in a few years’ time.”