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02 Jun 2021

A protein derived from a parasitic worm can induce immune cells with therapeutic potential

Mining secretions from a parasitic worm and using it to harness the immune system paints an interesting and squeamish picture – but a unique molecule found in this ‘excretory-secretory product’ could be a new therapeutic tool for a range of inflammatory diseases in humans.

There is anecdotal evidence that in areas where parasitic worms are prevalent, there are lower incidents of allergic and inflammatory disease. A lot of the worms excretory-secretory products are designed to enable it to persist in the intestine by switching off immune responses that would otherwise expel the parasite. Of particular interest to Dr Laura Cook, Doherty Institute Senior Research Officer, is that the worms can switch off immune responses by inducing regulatory T cells, or Tregs, which are an important immune cell population that help prevent autoimmune disease.

Dr Cook teamed up with Professor Rick Maizels and his laboratory at the University of Glasgow to investigate the therapeutic potential of a novel worm protein discovered by the Maizels lab that mimicked the function of a key controlling protein called TGFbeta.

“The protein secreted by the worm is a mimic of an important immune protein called TGFbeta. TGFbeta plays an important role in generating Tregs, which can dampen autoimmunity.” said Dr Cook.

“Tregs are now being investigated in several different diseases as cell therapies, but there have been a lot of issues with the stability of Treg cell products generated using TGFbeta that has restricted their clinical use.

“We found the parasite molecule-induced Treg cells were more stable, particularly in the presence of inflammation, compared to TGFbeta-induced Tregs. This could be a new approach to generate a cell therapy product that’s more effective for treating autoinflammatory diseases for example, inflammatory bowel disease.

“The next step is to investigate potential therapeutic applications and test those applications, whether it’s some kind of direct infusion of the parasite-derived molecule or the molecule-induced Treg cell product.

This work was conducted when Dr Cook was a postdoctoral researcher in Dr Megan Levings laboratory at the University of British Columbia in Vancouver, Canada.

Dr Cook has recently published these studies in humans, and as a co-author with study collaborators studies in mice in the journal Immunology and Cell Biology.

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