TURBO-charged immune cells could be key to boosting cancer therapies, according to a study by a team of Scottish scientists.
Researchers at the University of Edinburgh’s Centre for Inflammation Research have discovered a molecule called LL-37 that boosts the function of the immune cells, which trigger the body to attack tumours.
Their studies with mice have found the improved therapies produced a powerful anti-cancer immune response, which led to tumours shrinking. Initial experiments show the molecule has similar effects on human cells and could boost the success of cancer therapies for people.
LL-37 is produced naturally by the body in response to infections and helps to kill harmful bacteria and viruses.
The scientists found it also influences immune cells and boosts their function – in particular, that of specific cells which are responsible for initiating targeted immune responses – called dendritic cells. These have been used as cancer therapies because they can trigger other immune cells to recognise and attack tumours.
This type of approach typically involves taking a sample of the patients’ own cells and growing them under special conditions in the lab before infusing them back into the patient.
However, the process is expensive and has been hampered by difficulties with preparing sufficient numbers of dendritic cells which have the right characteristics for use as therapies.
The team found that adding LL-37 to dendritic cells while they are growing in the lab boosts yields of cells suitable for clinical use. Treating mice with cells grown in this way helped to shrink tumours and, in some cases, led to complete clearance of the cancer. Early tests suggest that LL-37 has similar effects on human cells but further work is needed, say the researchers.
The study, published in the journal Oncoimmunology, was funded by the Medical Research Council and the Royal Society.
Dr Emily Gwyer Findlay, of the Centre for Inflammation Research, said: “Our research has previously focused on the potential LL-37 has for fighting infections, but excitingly we now find that this substance, which the body makes naturally, could be used in new cancer treatments too.
“We hope that our discovery will create new opportunities by overcoming some of the current road-blocks to effective use of dendritic cell-based cancer therapies. This type of therapy, where dendritic cells are removed from patients and ‘improved’ in the lab then infused back in, has been used to most success in prostate cancer (in patients) and in mice to treat melanoma.
“We believe our peptide therapy could improve these therapies by supercharging the dendritic cells so that they know better where to travel to in the patient, and how to induce the immune system (T cells) to attack the tumour.
“However, because our treatment improves the dendritic cell response significantly, it opens up the possibility of treating cancers which up till now have not been able to be treated with this type of therapy, because the immune system does not see them so well.”
Dr Seth Coffelt from the Cancer Research UK Beatson Institute in Glasgow added: “This is an interesting improvement with this type of therapy, which is currently being used to treat certain types of cancers, such as prostate.
The scientists have created an easy and cost-effective way of boosting the communication ability of dendritic cells to drive an immune response from cancer-killing T cells.
“It would be interesting in future work to see if this approach could improve T cell response in other cancer types,” he added.
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