Researchers have found they can cut off a sleep-switch and wake up immune cells to hunt down and destroy cancer, according to research published today.
The PD-1 switch normally acts as a safety device by stopping immune cells from attacking things they shouldn’t, such as healthy human cells. However, cancer cells exploit this switch to hide from the immune system and avoid attack.
This latest research, published in Cancer Research, could lead to more targeted therapies which don’t cause the severe side effects associated with the immunotherapy drugs called checkpoint inhibitors which have been used to block these signals.
A team led by Professor Karl Peggs and Dr Sergio Quezada used a gene editing technique to remove the PD-1 switch from T cells (a type of immune cell or white blood cell which fight off infection in the body) found in the tumour. The researchers found that the immune system was now able to wipe out the cancer cells which no longer had control over the T cells.
This study was carried out on mice in the laboratory. Researchers took T cells from the tumour, removed PD-1, multiplied the T cells and put them back into the mice and found that the tumours shrank. The next step will be to test this approach in clinical trials at the NIHR/Wellcome UCLH Clinical Research Facility.
Dr Quezada said: “This is an exciting discovery and means we may have a way to get around cancer’s defences while only targeting the immune cells that recognise the cancer. While drugs that block PD-1 do show promise, this method only knocks out PD-1 on the T cells that can find the tumour which could mean fewer side effects for patients.”
The study was supported by the Experimental Cancer Medicine Centres Network – an initiative funded in partnership between Cancer Research UK and the four Health Departments of England, Scotland, Northern Ireland, and Wales; and published in Cancer Research.
Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “We know that some cancers can switch off the cells of our immune system, and this interesting laboratory research suggests a new way that we might be able to get around the problem, although this is still some way away from use in the clinic.”
Professor Peggs’ research with patients is supported by the BRC and the NIHR Blood & Transplant Research Unit in Stem Cells and Immunotherapies.
To read TALEN-mediated inactivation of PD-1 in tumor-reactive lymphocytes promotes intratumoral T cell persistence and rejection of established tumors visit the Cancer Research journal website.
