Combination Cell-gene Therapy for Lung Cancer to be Tested in UK Patients

A pioneering new combined cell-gene therapy to treat lung cancer will be tested in NHS patients this year, after receiving £2m of Biomedical Catalyst funding from the Medical Research Council (MRC).

Researchers led by Professor Sam Janes at UCL/UCLH will carry out the first UK clinical trial of a combined stem cell and gene therapy for the disease which kills around 34,000 people a year in the UK.

The treatment uses stem cells as a delivery vehicle for a potent anti-cancer gene, which induces a self-destruct pathway in cancer, but not healthy cells.

Early tests of the experimental treatment in mice have shown it can reduce and in some cases clear tumours. The team will now test the treatment in human volunteers, firstly to check that the treatment is safe and then in 56 lung cancer patients to see how effective the gene/cell therapy plus chemotherapy is compared with standard care.

Principle Investigator Sam Janes, a Wellcome Trust Senior Research Fellow and Professor of Respiratory Medicine at UCL and Consultant in Respiratory Medicine at UCLH, said:

“Lung cancer is very difficult to treat because the vast majority of patients are not diagnosed until the cancer has spread to other parts of the body. One therapy option for these patients is chemotherapy, but even if successful this treatment can normally only extend lives by a handful of months. Chemotherapy can also cause widespread toxic side-effects.

“We aim to improve prospects for lung cancer patients by using a highly targeted therapy using stem cells, which have an innate tendency to home to home in on tumours when they’re injected into the body. Once there, they switch on a ‘kill’ pathway in the cancer cells, leaving healthy surrounding cells untouched. If clinical trials are successful, our treatment could be transformative for the treatment of lung cancer, and possibly other types of tumour in future.”

The therapy works by modifying donor stem cells so that they express an anti-cancer gene called TRAIL*. Being encased within a cell protects the genetic material from being degraded by the body so that when it reaches the tumour it is able to trigger a signalling pathway that kills the cancer cells.

Each patient in the trial will receive almost a billion cells over three infusions, three weeks apart (injected one day after they receive chemotherapy). Over the next three years 100 billion cells will be created at the Royal Free Hospital’s £2.1 million, state-of-the-art cell manufacturing lab, which is run by Dr Mark Lowdell, director of cellular therapy and biobanking at the Royal Free London NHS Foundation Trust.

A key advantage of the treatment is that the cells can be used ‘off the shelf’ and do not need to be from a close relative or tissue match. This is because they have relatively few proteins on the surface and do not induce an immune response in the recipient.

The clinical trial is being funded through the Biomedical Catalyst, a programme managed jointly by the MRC and Innovate UK to bridge the funding gap between discovery science and commercial development, which helps to bring new treatments and technologies to patients faster.

Dr Chris Watkins, Director of Translational Research who oversees the Biomedical Catalyst at the MRC, said:

“Lung cancer kills more men and women than any other cancer and improving the outcome for patients with this terrible disease is one of the biggest challenges we face. This new therapy, which uses modified stem cells to target the tumour directly is truly at the cutting edge and will draw on the UK’s unique position as a leader in the field of cell-based therapies.”

Further information

^*Tumour Necrosis Factor related Apoptosis-Inducing Ligand (TRAIL)

The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. www.mrc.ac.uk

About UCL (University College London) Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. We are among the world's top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 35,000 students from 150 countries and more than 11,000 staff. Our annual income is more than £1 billion. www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our YouTube channel YouTube.com/UCLTV

The Wellcome Trust is a global charitable foundation dedicated to improving health. We support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine. Our investment portfolio gives us the independence to support such transformative work as the sequencing and understanding of the human genome, research that established front-line drugs for malaria, and Wellcome Collection, our free venue for the incurably curious that explores medicine, life and art.

About the Royal Free London NHS Foundation Trust

The Royal Free began as a pioneering organisation and continues to play a leading role in the care of patients. Our mission is to provide world class expertise and local care. In the 21st century, the Royal Free London continues to lead improvements in healthcare.

The Royal Free London attracts patients from across the country and beyond to its specialist services in liver, kidney and bone marrow transplantation, haemophilia, renal, HIV, infectious diseases, plastic surgery, immunology, vascular surgery, cardiology, amyloidosis and scleroderma and we are a member of the academic health science partnership UCLPartners. In July 2014 Barnet Hospital and Chase Farm Hospital became part of the Royal Free London. For further information, visit www.royalfree.nhs.uk

UCLH(University College London Hospitals NHS Foundation Trust), situated in the West End of London, is one of the largest NHS trusts in the United Kingdom and provides first-class acute and specialist services. The state-of-the-art University College Hospital which opened in 2005, is the focal point of UCLH alongside five cutting-edge specialist hospitals. UCLH is committed to research and development and forms part of UCL Partners which in March 2009 was officially designated as one of the UK's first academic health science centres by the Department of Health. UCLH works closely with UCL, translating research into treatments for patients. Visit our website www.uclh.nhs.uk, we are also on Facebook (UCLHNHS), Twitter (@UCLH) and Youtube (UCLHvideo).