Our funding in action

Fund backs cancer vaccine trial

JHMRF funded research into using the body’s own immune system to fight mesothelioma is proceeding to a clinical trial. Fund trustees said they were delighted that the laboratory work carried out by Dr Zsuzsanna Tabi’s team of cancer immunologists at Cardiff University was moving into an exciting new phase with trials of an experimental cancer vaccine.

Dr Tabi has established a partnership with Dr Jason Lester, an oncologist at Velindre Cancer Centre in Cardiff, and UK biotech company, Oxford BioMedica to study the effects of the experimental cancer vaccine TroVax® in mesothelioma. A feasibility study funded by the JHMRF will begin in the autumn using TroVax® in combination with first-line chemotherapy agents Alimta and Cisplatin.

JHMRF trustee Dr Kate Hill said, “The Cardiff immunology team is well established in their field and has shown a tremendous commitment to working with us to pursue research in mesothelioma, and we are delighted to continue our association with Dr Tabi and her colleagues. There are never guarantees in any type of experimental research but we believe that immunotherapy has potential in the treatment of mesothelioma.”

Oxford BioMedica Chief Scientific Officer Stuart Naylor said, “The pioneering work undertaken by Dr. Tabi and her colleagues have identified 5T4 as an exciting new therapeutic target in mesothelioma, a disease which has few treatment options available to patients.

“Oxford BioMedica is happy to be able to supply TroVax® for this phase I/II clinical study in mesothelioma patients and we are very pleased to be able to work with the June Hancock fund and colleagues at the Velindre hospital.”

Therapeutic cancer vaccines can be used in a number of ways. They can be injected into patients to stimulate the body’s own defence system to produce immune cells and antibodies which will attack the cancer cells by targeting specific markers (antigens) on them.

Immunotherapy may offer new ways of attacking cancer cells by targeting the unique markers on cancer cells, and by using the patients’ own immune cells and treat them in the laboratory to fight cancer cells more effectively, before injecting them back into the patient.

TroVax® is a cancer vaccine which targets 5T4, a protein expressed on most common tumour types and which has recently been shown to be present on mesothelioma cells by DrTabi and her colleagues. TroVax® has been shown to be safe and effective at inducing immune responses in other types of cancer but this study will be the first time that it will be used in mesothelioma in the UK.

The Fund is constantly seeking to advance the range and type of treatments on offer to patients by supporting high quality research and exploring novel approaches to therapy.

US biotech company Dendreon recently became the first to have a cancer vaccine approved by the US drug licensing agency but more research is needed to make immunotherapy part of standard-of-care in cancer treatment.

Webber researches exosome link

The Fund has awarded £23,000 for a promising strand of investigation into cells associated with mesothelioma at the Velindre Cancer Centre in Cardiff. The two-year project is being carried out by Dr Jason Webber of the Exosome Biology Group, led by Dr Aled Clayton. Dr Webber said, “There is significant interest in this realm of cancer research and, naturally, we hope it will lead to potential new treatments. I am very grateful to the Fund for giving me the opportunity to pursue this important work.”

Dr Webber’s research focuses on small bubbles of fat, called exosomes, produced by cancer cells. The Velindre team has already shown how exosomes produced by mesothelioma cells can block the body’s own immune system, therefore weakening its natural defence against cancer.

Dr Webber is exploring a different process; the effect of mesothelioma-exosomes on non cancerous cells called fibroblasts. These form a large part of normal tissue, but become strongly activated following exposure to mesothelioma exosomes. This activation in the tumour environment is often associated with poor prognosis for many cancer types.

The team has identified a protein (Transforming Growth Factor-beta or TGF_) on the surface of the exosomes which is responsible for activating fibroblasts. Dr Webber has already found a new way of constraining this activity and preventing the fibroblasts from being activated; his research will explore the potential for treatments based on these findings.

Fellowship explores new anti-meso compound

The Fund’s first fellowship award to a team from Queen Mary College London will investigate a new biological compound known to act against mesothelioma cells. Named in honour of our greatest fundraiser, Steve Lee, the doctoral fellowship has been awarded to PhD student Seble Lemma and her supervisor Dr Adrian Dobbs.

They will be synthesising a naturally-occurring bacteria (JBIR-23) found in soil and vegetation to see if it could be used as a treatment for the disease.  It’s the first product that’s demonstrated significant activity against mesothelioma, so this work is potentially very important.

Steve Lee and his wife Ros raised over £55,000 for the Fund with huge support from his running club, Reading Roadrunners.  Steve lost his fight in January 2011, but his work lives on at Queen Mary’s and collaborators St Bartholomew’s hospital.

Fund trustee Kimberley Stubbs said, “Steve was such a positive person, facing his illness with dignity and determination to raise as much money for mesothelioma research as possible. And boy did he do well! With his beloved wife Ros always by his side, Steve raised over £55,000, with friends and colleagues from the Reading Roadrunners Club supporting him throughout.”

Steve and Ros were delighted to meet Seble’s PhD supervisor Dr Adrian Dobbs of Queen Mary College, University of London last year, and learn as much as they could about the project. A former journalist, Steve asked many questions, reassuring both himself and Ros that the results of their fantastic fundraising efforts were being well spent.

“We saw at first hand the huge love and affection in which Steve was held at the Roadrunners annual dinner last year,” added Kim. “He was a remarkable man, he will never be forgotten, and he leaves behind a legacy for others – just what he wanted to do.”

Ros joined trustees Kate Hill and Vanessa Bridge for an update from Dr Dobbs and Ms Lemma at QMC last May. The project is going well, with work due to be completed on synthesising the first parts of the JBIR-23 molecule; they will be handed over for testing to molecular biologists to see how effective they are in killing mesothelioma cells.

Adrian Dobbs’ professional interest in mesothelioma began in personal tragedy; he too, lost his father to the disease, following his exposure to asbestos as a civil engineer on visits to underground tunnels in London. Dr Dobbs said: “At this time, towards the end of the 1950s, people were working without any protection against asbestos at all, despite the risks – it’s awful to think about that.

“Ever since I became a chemist I have been looking for ways of using my knowledge in the fight against mesothelioma, so I am honoured to be involved in this project.”

Colorado showcase for immunologist

Dr Saly Al-Taei is working on a JHMRF-funded project on ways of stimulating patients’ immune systems into recognising and killing mesothelioma. The Fund enabled her to present a poster at a major conference in Keystone, Colorado earlier this year on the cellular and molecular biology of immune escape in cancer. Dr Al-Taei said, “My poster on tumour-associated suppressor cells in malignant pleural mesothelioma attracted a lot of mixed interest from delegates.

“Some were intrigued by our data on the immunological profile of the cancer and the pleural fluid environment and encouraged by the development of immunotherapies for mesothelioma. It’s also fair to report that there was scepticism, that this aggressive disease is beyond any medical intervention and funding for future research will be difficult due to the life expectancy and occurrence rate of mesothelioma.

“Unfortunately, we are all too aware that mesothelioma research will always struggle to compete with the more common and well publicised cancers such as breast and prostate and it certainly made me appreciate the work of JHMRF in funding mesothelioma research.”

There was particular interest at the conference in two aspects of the team’s research; firstly, in the use of patient samples, which is relatively rare in America, where research is predominantly conducted on mice. Delegates were also extremely interested in the prospect of clinical trials involving patients getting underway later this year.

Dr Al-Taei added, “If you put the altitude sickness, below freezing temperatures and American portion sizes aside, it was a great conference. I learned a lot about potential obstacles to immunotherapy which we will take into consideration for our clinical trial and also gained some interesting ideas for future direction of my research. I am extremely grateful for the Fund for helping me attend this conference and especially for funding my current research which has now been translated into a clinical trial in patients.”

Disease claims lives worldwide

A Fund travel grant also enabled Zsuzsanna Tabi to attend the 10thconference of the International Mesothelioma Interest Group in Kyoto, Japan in September 2010. She was presenting findings from the T-cell work she is carrying out with funding from the JHMRF, and introduced the forthcoming clinical trial testing a cancer vaccine with standard chemotherapy.

The conference heard that the UK features high up the World Health Organisation’s mortality database for recorded deaths from mesothelioma, with 28,400 to date (the USA has 36,600 and Italy 18,500). More than 174,300 deaths from mesothelioma were recorded by the 56 contributing 
countries between 1994-2008, although the real figure will of course be higher, and the average rate of increase incidence is 5.6% for men and 3.4% for women (source: review by Ken Takahasi, Japan).