British researchers have found a new way to identify immune cells capable of detecting tumors — opening a path to treatments that could trigger the body's natural defenses to wipe out cancer.
The discovery by scientists at University College, London promises to bring greater precision to the new generation of "cancer immunotherapies", which have been generating excitement as the most important breakthrough in oncology for decades.
Immunotherapies, which aim to help patients' disease-fighting T-cells hunt and destroy tumours, have been shown to extend the lives of some people with advanced forms of cancer for months or years. But the first of these drugs to reach the market only work in about a third of patients.
The research could open the way to increase response rates by identifying T-cells that can reach every tumour cell — rather than just a subset — leading to more potent therapies.
Working with academics across the US and Europe, the UCL scientists sought to understand how the immune system could keep track of the constant genetic mutations in tumour cells that make the disease so hard to treat.
They found that some of the earliest mutations produced antigens — the tell-tale signs of disease that activate the immune system — that were displayed in all subsequent mutations.
This in itself does not provide a silver bullet because cancer cells use a range of tricks to defend themselves against attack.
However, by finding a way to identify antigens that are ubiquitous in tumours and detectable by T-cells, the research could aid development of immunotherapies that disable these defenses.
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Sergio Quezada, co-author of the study published in the journal Science on Thursday, likened the breakthrough to a technology that allowed police to catch all criminals at once.
"Genetically diverse tumors are like a gang of hoodlums involved in different crimes — from robbery to smuggling. And the immune system struggles to keep on top of the cancer — just as it's difficult for police when there's so much going on.
"Our research shows that instead of aimlessly chasing crimes in different neighbourhoods, we can give the police the information they need to get to the kingpin at the root of all organised crime — or the weak spot in a patient's tumour — to wipe out the problem for good."
The research, funded by Cancer Research UK and the Rosetrees Trust, involved analysis of data from hundreds of cancer patients to identify common antigens displayed by tumors. Scientists then took T-cells from two patients with lung cancer and carried out laboratory experiments to find those that could recognise all the antigens.
Charles Swanton, co-author of the report and a scientist at the Francis Crick Institute as well as UCL, said this exercise would need to be carried out for every individual patient because every tumor is unique. "This...takes personalised medicine to its absolute limit where each patient would have a unique, bespoke treatment."
Peter Johnson, chief clinician of Cancer Research UK, said the treatments were likely to come in the form of cell therapies and vaccines that aim to boost the number and effectiveness of T-cells present in tumours. These could work in combination with the first generation of immunotherapies, known as checkpoint inhibitors, which remove the blockade that prevents T-cells attacking tumours.
Clinical trials of the first therapies based on the UCL research could start within two years, Prof Johnson predicted. "It gets us closer to knowing why some patients respond to immunotherapy treatment and others don't, and how we might select which patients will benefit the most," he added.
The personalized nature of the treatments meant they were likely to be very expensive at first, Prof Swanton said. But he hoped they would eventually prove more cost-effective than current cancer drugs because the benefits would last for longer. The 71 cancer drugs approved by US regulators in the past 12 years have produced a median survival rate of just 2.1 extra months of life at an average cost of $10,000 per month, said Prof Swanton.