Take off immune system brake to improve cancer vaccines

The discovery of a new molecule that can act as a brake for the immune system could lead to new therapies for cancer and autoimmune diseases such as diabetes.
A team of scientists at St Jude Children's Research Hospital claims to have discovered a protein complex composed of Epstein-Barr-virus-induced gene 3 (Ebi3) and the p53 subunit of interleukin-12 alpha (IL-12 alpha) that is produced by regulatory T cells to suppress immune system activity.The newly reconised complex has been dubbed interleukin-35 (IL-35) and is one of the few signalling molecules - called cytokines - that inhibits, rather than stimulates, the immune system. Given that one of the ways cancer tumours survive is through blocking immune system responses, stopping IL-35 from functioning may help kill them.

"Treatments that block IL-35 activity may make anti-cancer vaccines more effective and provide new therapeutic opportunities for autoimmune and inflammatory diseases," said Dr Dario Vignali, associate member in the St Jude Department of Immunology, and senior author of a paper published in Nature today.Regulatory T cells are also essential for preventing autoimmune diseases and for limiting inflammatory diseases such as asthma and inflamatory bowel disease and so manuipulating IL-35 could also provide treatments for these diseases."Our findings suggest that controlling levels of IL-35 in patients might one day allow clinicians to dial the immune response up or down depending on the needs of the patient," said Dr Lauren Collison, another of the scientists involved in the work.Professor Foo Liew's group at the University of Glasgow has also working on IL-35 for the past four years and have a patent on the molecule.
Prof. Liew explained that although they were the first to publish the name IL-35 in an article in the European Journal of Immunology in September, a month earlier, Vignali had also used the term at a conference."We have reported that IL-35 can be used to treat arthritis and suggested that it could be a potent drug for treating a range of diseases, including multiple sclerosis, colitis, diabetes and transplantation rejection by putting a brake on the immune system," Liew told Drug Researcher.com."Alternatively, antidote of IL-35 may be used to boost our immune response to fight cancers and infections. We are in collaborations with a number of pharmaceutical companies to develop these drugs," he added.Their work in mice has suggested that IL-35 can increase the production of regulatory T cells and thus suppressed the activity of aggressive effector T cells.They also found that the complex can prevent the development of a third type of T cell, called TH17 cells, which increase inflammation by producing the cytokine, IL-17.

By staff reporter

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