Hope for threatened Tasmanian devils

(Press-News.org) New research paves the way for the development of a vaccine for the Tasmanian devil, currently on the brink of extinction because of a contagious cancer.

It has been less than two decades since scientists discovered the contagious cancer devil facial tumour disease (DFTD) which causes 100 per cent mortality in the endangered marsupials. The facial cancer, which spreads when the devils bite each other's faces during fighting, kills its victims in a matter of months. As it has already wiped out the majority of the population with sightings of devils reduced by 85 per cent, scientists are desperate to find out more about the mysterious cancer which somehow manages to evade the devils' immune system.

Until now, scientists have believed that the tumours were able to avoid detection by the immune system because the Tasmanian devils have very little genetic diversity (preventing the immune system from recognising the tumour as foreign). However, a University of Cambridge led collaboration with the Universities of Tasmania, Sydney and South Denmark has discovered that the explanation is more complex.

On the surface of nearly every mammalian cell are major histocompatibility complex (MHC) molecules. These molecules enable the immune system to determine if a cell is friend or foe, triggering an immune response if the cell is foreign and a potential threat. The new research, published today, 11 March, in the journal PNAS, reveals that DFTD cancer cells lack these critical molecules, thereby avoiding detection by the devils' immune system.

Professor Jim Kaufman, from the University of Cambridge's Department of Pathology, said: "Once it was found that the cancer was escaping from the devils' immune system, scientists needed to figure out how."

The researchers found that the DFTD cells have lost the expression of MHC molecules, but that the genes that code for these molecules are still intact. This means that these genes could potentially be turned back on. Indeed, the scientists showed that by introducing signalling molecules such as interferon-gamma, a protein which triggers the immune response, the DFTD cells can be forced to express MHC molecules.

Dr Hannah Siddle, lead author of the paper from the University of Cambridge, said: "Developing a vaccine based on our research could tip the balance in the favour of the devil and give them a fighting chance."

"However, we still face some hurdles. The tumour is evolving over time and any vaccine programme would have to take this into consideration. Also, because of the difficulties of vaccinating a wild population, it may be more efficient to use a vaccine in the context of returning captive devils to the wild."

Although the only other contagious cancer has been found in dogs (canine transmissible venereal cancer), the rapid development of DFTD highlights how quickly they can emerge.

Professor Kaufman added: "Our study has implications beyond the Tasmanian devil. Sooner or later a human strain of contagious cancer will develop, and this work gives us insight into how these diseases emerge and evolve."

### The research was funded by the Wellcome Trust.

For additional information please contact:
Genevieve Maul, Office of Communications, University of Cambridge
Tel: direct, +44 (0) 1223 765542, +44 (0) 1223 332300
Mob: +44 (0) 7774 017464
Email: Genevieve.maul@admin.cam.ac.uk

Notes to editors:

1. The paper 'Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease' will be published in the 11 March edition of PNAS.

2. Images and video are available from the following website: https://picasaweb.google.com/100113643990790184358/TasmanianDevils?authuser=0&authkey=Gv1sRgCMyHpquclbTCOA&feat=directlink

3. University of Cambridge: The University of Cambridge's mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.

4. The University of Tasmania is the fourth oldest university in Australia, established in 1890. Ranked in the top 3 per cent of universities globally and in the top 10 Australian research universities, the University has a long-standing reputation for excellence in learning, teaching and research. In 2015, UTAS will celebrate 125 years of achievement and contribution to Tasmania, Australia and the global community.

5. Save the Tasmanian Devil Program: The Save the Tasmanian Devil Program is the official response to the threat of DFTD to the survival of the Tasmanian devil, and is a joint initiative of the Australian and Tasmanian Governments. Its mission is to ensure the survival of the Tasmanian devil as an ecologically functioning entity in the Tasmanian ecology. The Program is encouraged by the results of the study by Hannah V. Siddle et al, which show how the tumour cells evade detection by the devils' immune system. In the long-term, these results may be a vital pre-cursor to the development of a vaccine for the devil against the deadly cancer. In the meantime, the Save the Tasmanian Devil Program has established an insurance population of over 500 disease free devils in captive breeding facilities throughout Australia to prevent the species' extinction. The Program is also working on establishing populations of healthy wild devils in large areas of natural habitat in Tasmania, like islands and peninsulas that can be isolated from diseased devils to ensure the survival of the species in the wild. For further information please go to http://www.tassiedevil.com.au 6. The University of Sydney is a leading, comprehensive research and teaching university committed to the transformative power of education and to teaching greater knowledge and understanding of the world and its people. It aims to create and sustain a community in which – for the benefit of both Australia and the wider world – the brightest researchers and the most promising students, whatever their social or cultural background, can thrive and realise their full potential. 7. Menzies Research Institute Tasmania, an institute of the University of Tasmania, is one of Australia's leading health and medical research institutes.Menzies is renowned internationally for its innovative research that utilises the unique competitive advantages Tasmania offers, including our island geography, stable population and our extensive genealogical records. For over 25 years, significant breakthroughs have been made by Menzies scientists in the understanding, prevention and treatment of a number of diseases. Menzies focuses on a range of common diseases within Tasmania including arthritis, cancer, dementia, diabetes, cardiovascular disease, mental health and multiple sclerosis. For further information please go to http://www.menxies.utas.edu.au