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Cancer genetics discovery could revolutionise treatment

7 March 2016
Appeared in BioNews 842

Scientists have identified a method by which all the cells in a tumour could potentially be recognised and eradicated by the patient's own immune system.

The findings, published in Science, have been described as a major advance in the field of cancer immunotherapy and could lead to development of personalised treatment for cancers, even at their most advanced stages. However, any such intervention might be expensive and the procedure has not yet been trialled in patients, explains BBC News.

As tumours grow and evolve they carry with them a number of biological 'flags' known as antigens, which can potentially be recognised and targeted by the patient's immune cells. However, as the tumour develops, unique mutations can appear in different areas, resulting in a highly complex, composed of mixed populations of cells with different genetic make-ups. The more advanced the cancer, the more complex the tumours are.

Attempts so far to reactivate the body's immune cells, known as T cells, to target cancer cells have not been shown to work in everyone. Individual tumour cells will also often have different responses to the same drug. However, by examining data from hundreds of patients in previous cancer studies, a collaboration of scientists from the UCL Cancer Institute and the Francis Crick Institute in London have identified a set of antigens from the earliest version of the tumour that is common to all tumour cells.

They found that cancer cells evolve by 'branching', so have a 'trunk' of shared mutations from which they change, splitting off in separate directions. The mutations within the 'trunk' are shared by all tumour cells and lead to the appearance of a certain number of shared antigens on the surface of the cells. The researchers were able to isolate T cells from two patients with lung cancer that were able to recognise common antigens present in all the tumour cells.

'Now we can prioritise and target tumour antigens that are present in every cell - the Achilles heel of these highly complex cancers,' said Professor Charles Swanton, one of the lead authors.

The researchers believe they can potentially reactivate T cells to target tumours and introduce these by developing a vaccine or by taking the patients own cells and reintroducing them. This would result in personalised treatments unique to each patient with T cells tailored to recognise the 'trunk' antigens specific to that particular patient's tumour.

Professor Peter Johnson, of Cancer Research UK, which funded the study along with the Rosetrees Trust, said: 'This fascinating research gives us vital clues about how to specifically tailor treatment for a patient using their immune system.'

Immunotherapy is still a relatively new field, and whether or not the treatments will work is unclear. Professor Swanton hopes to launch the first clinical trial in lung cancer patients within the next three years.

'We haven't proved that this can impact on patient care. What we have shown is that there are unique therapies potentially present within each patient's tumour,' he explained. 'This is taking personalised medicine to its absolute limit.'

Cancer's 'Achilles' heel' discovered by British scientists raising hope of 'cure'
The Independent |  3 March 2016
Cancer tumour genetics reveal possible treatment revolution
The Guardian |  4 March 2016
Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade
Science |  3 March 2016
Scientists 'find cancer's Achilles heel'
BBC News |  4 March 2016
Tumours contain the seeds of their own destruction
Cancer Research UK (press release) |  4 March 2016
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