Cutting off a sleep-switch on immune cells inside a tumour wakes up the cells and enables the immune system to hunt down and destroy the disease, according to a new Cancer Research UK-funded study published in Cancer Research.
Cancer cells exploit this switch to hide from the immune system and avoid attack. Immunotherapy drugs known as checkpoint inhibitors also block these signals and have already been used to treat patients. But in doing so they affect the whole of the immune system, which can cause severe side effects in some patients.
The team from University College London’s Cancer Institute led By Professor Karl Peggs and Dr Sergio Quezada used a gene editing technique to remove the switch – called PD-1 – from T cells** found in the tumour. They 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. The 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.
The PD-1 switch – found on T cells – is normally a safety device that stops the immune cells from attacking things they shouldn’t, such as healthy human cells.
Dr Sergio Quezada, Cancer Research UK scientist and co-lead author from University College London’s Cancer Institute, 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.”
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”
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* Menger et al., TALEN-mediated inactivation of PD-1 in tumor-reactive lymphocytes promotes intratumoral T cell persistence and rejection of established tumors. Cancer Research, 2016.
** T- cells are a type of immune cell or white blood cell which fight off infection in the body.
The study was also funded by a EU FP7 grant. Professor Karl Pegg’s research with patients is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. It was also supported by the Experimental Cancer Medicine Centres (ECMC) Network – an initiative funded in partnership between Cancer Research UK and the four Health Departments of England, Scotland, Northern Ireland, and Wales.