Researchers are working flat out to convert a discovery hailed as cancer's ‘Achilles' heel’ into a treatment that they hope can be tested on humans in two years.
Earlier this month, the UK-based consortium, which also includes Cancer Research UK and the Francis Crick Institute, said in a research paper published in Science, that they had found a way of identifying unique markings within tumours that would allow the body’s own immune cells to target the disease.
Now, they are building on their recent discoveries, moving towards a clinical trial which they hope can happen in the next two years.
‘We want to understand the antigens – these flags that the immune system can find on tumour cells – in greater detail and we will use an animal model to study cancer evolution so that we can develop a clinical trial around our observations,’ said Professor Charles Swanton from University College London, UK, who led the work.
However, while the new findings are an important step forward in how we think about treating cancer and have opened the door to the development of personalised treatments, we are still a decade away from a game-changing new therapy and this does not represent a cure, Prof. Swanton said.
‘Cancer evolution is a force to be reckoned with.’
Professor Charles Swanton, University College London, UK
One of the reasons cancer has been such a stubborn foe is its ability to change or ‘mutate’. For decades, doctors thought of tumours as deadly lumps of tissue made up of identical cancer cells.
What was not well understood until more recently is that tumours are constantly evolving and are, in fact, made of several different types of cancer cell. This ability to mutate makes cancer a moving target.
‘Essentially, cancers evolve over space and time,’ says Prof. Swanton, who leads the THESEUS project to investigate cancer evolution, which is supported by the EU’s European Research Council.
‘Because a single tumour can have billions of different cells each with subtly distinct genomic changes, sharing a common ancestor, a single tissue biopsy can be misleading – you might not get the whole picture.’
Tree of life
Prof. Swanton’s team set out to understand how cancers evolve so that new therapies could be developed. ‘We know that cancer evolution is a force to be reckoned with, but the field lacks the tools to understand its full implications,’ he said.
‘Our task is to model these changes so that we can develop new therapeutic approaches that limit this evolution.’
Central to this approach is an understanding that dates back to Charles Darwin, where genetic evolution can be viewed as a tree with each branch representing a new set of mutations. To tackle cancer tumours, Prof. Swanton’s team decided to attempt to identify means of targeting the tree ‘trunk’ - mutations that are present in every tumour cell.
‘Mutations in the trunk of the tumour’s evolutionary tree, present in every tumour cell, could serve as flags to the immune system, helping the body to identify and attack all tumour cells within the body,’ explained Prof. Swanton. ‘The next step would be to see if we can awaken the body’s immune cells to these flags which are present in every tumour cell.’
He says the body already has powerful immune cells known as T-cells which can recognise these flags. By removing some of these cells that recognise these common flags, expanding their number in a lab and putting them back into the body, the chances of the immune system successfully destroying the tumour may be enhanced.
This is where ‘personalisation’ comes in. Because the immune cells would be those of the individual cancer patient, each patient’s treatment would be completely unique. Commentators have said that this would be very expensive and time-consuming at first but, like most innovations, should become cheaper and faster over time.
‘This is really fascinating and takes personalised medicine to its absolute limit, where each patient would have a unique, bespoke treatment,’ said Prof. Swanton.
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Re-engineering immune cells and modifying yeast to produce drugs are just two potential applications, says Prof. Toni Cathomen.