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Gene therapy could 'turn off' severe allergies

A single treatment giving life-long protection from severe allergies such as asthma could be made possible by immunology research at The University of Queensland.


A single treatment giving life-long protection from severe allergies such as asthma could be made possible through immunology research at The University of Queensland. A team led by Associate Professor Ray Steptoe PhD, at the UQ Diamantina Institute has been able to 'turn-off' the immune response which causes allergic reaction in animals.

"When someone has an allergy or asthma flare-up, the symptoms they experience results from immune cells reacting to protein in the allergen.

"The challenge in asthma and allergies is that these immune cells, known as T-cells, develop a form of immune 'memory' and become very resistant to treatments. We have now been able to 'wipe' in animals the memory of these T-cells with gene therapy, de-sensitising the immune system so that it tolerates the protein.

"Our work used an experimental asthma allergen, but this research could be applied to treat those who have severe allergies to peanuts, bee venom, shell fish and other substances."


Ray Steptoe PhD, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.


The research is published in JCI Insight. The next step is to to replicate these results using human cells in the laboratory.

Dr Steptoe explains: "We take blood stem cells, insert a gene which regulates the allergen protein and we put that into the recipient. Those engineered cells produce new blood cells that express the protein and target specific immune cells, 'turning off' the allergic response."


The eventual goal is a single injection gene therapy, replacing short-term treatments that target allergy symptoms.


"We haven't quite got it to the point where it's as simple as getting a flu jab, so we are working on making it simpler, safer and to be used across a wide cross-section of affected individuals," Dr Steptoe adds. "At the moment, the target population might be those individuals who have severe asthma or potentially lethal food allergies."

Dr Steptoe's research has been funded by the Asthma Foundation and the National Health and Medical Research Council. Asthma Foundation of Queensland and New South Wales, Chief Executive Officer Dr. Peter Anderson has said more than two million Australians have asthma, and current statistics show that more than half of those are regularly burdened with symptoms of their disease.

The Foundation welcomes the findings of this research and looks forward to a day in the future when a safe one-off treatment may be available with the potential to eliminate any experience of asthma in vulnerable patients.

Abstract
Memory Th2 cell responses underlie the development and perpetuation of allergic diseases. Because these states result from immune dysregulation, established Th2 cell responses represent a significant challenge for conventional immunotherapies. New approaches that overcome the detrimental effects of immune dysregulation are required. We tested whether memory Th2 cell responses were silenced using a therapeutic approach where allergen expression in DCs is transferred to sensitized recipients using BM cells as a vector for therapeutic gene transfer. Development of allergen-specific Th2 responses and allergen-induced airway inflammation was blocked by expression of allergen in DCs. Adoptive transfer studies showed that Th2 responses were inactivated by a combination of deletion and induction of T cell unresponsiveness. Transfer of BM encoding allergen expression targeted to DCs terminated, in an allergen-specific manner, Th2 responses in sensitized recipients. Importantly, when preexisting airway inflammation was present, there was effective silencing of Th2 cell responses, airway inflammation was alleviated, and airway hyperreactivity was reversed. The effectiveness of DC-targeted allergen expression to terminate established Th2 responses in sensitized animals indicates that exploiting cell-intrinsic T cell tolerance pathways could lead to development of highly effective immunotherapies.

JMDís present address is: School of Biomedical Science, Queensland University of Technology, Brisbane, Australia. Conflict of interest: The authors have declared that no conflict of interest exists. Reference information:JCI Insight. 2017;2(11):e85742. https://doi.org/10.1172/jci.insight.85742.


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Jun 6, 2017   Fetal Timeline   Maternal Timeline   News   News Archive   

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