Leanne Reynolds, Head of Research at PCUK said:

For people diagnosed with pancreatic cancer there are very limited treatment options due to the complex nature of the disease. Surgery is the only treatment which could save lives but only around 10% of people with pancreatic cancer will be able to have it.

We urgently need a new approach to treating pancreatic cancer which is why we’re delighted to be funding this ground-breaking new research into immunotherapy. CAR T cell immunotherapy is exciting because it is showing positive results in other cancers. That’s why we’ve called this award the ‘Grand Challenge’ – because we’re hopeful that CAR T cell therapy will also work in pancreatic cancer, and potentially offer new treatment options for patients.

We are incredibly grateful for all our supporters, who have helped us fund Professor Nick Lemoine and his team to hopefully develop this much-needed new treatment for pancreatic cancer

Pancreatic cancer is diagnosed in just over 9,900 people in the UK annually. Sadly, 90% of the individuals affected lose their lives each year, and less than 1% of patients survive the disease for 10 or more years.

Immunotherapy harnesses the body’s own immune system to identify and kill cancer cells, and has been demonstrated to be an effective treatment option in a variety of cancer types. In CAR T cell therapy, T cells- key immune cells responsible for fighting infected cells- are isolated from patient blood samples, modified outside of the body and reinjected back into the patient. Once back in the body, the T cells are equipped to target and attack tumours.

Breaking through the barrier

CAR T cell therapy has proven to be effective against some blood cancers; however, solid cancers have demonstrated resilience to this treatment. Pancreatic tumours are notoriously difficult to treat. The tumours are surrounded by dense, fibrous tissue, which creates a physical barrier around the tumour and inhibits the infiltration of drugs at the site. In addition, the tumours are hypovascularised, meaning that they have very few blood vessels. As a result, there is a limited blood supply to carry immune cells and drugs to the tumour site.

The team endeavour to overcome these challenges and, if successful, hope to improve the outcome for those suffering with pancreatic cancer.

The Grand Challenge

The project will focus on three main areas:

1) Generating CAR T cells that are able to target and kill pancreatic cancer cells.  Once isolated from patient blood samples, T cells are engineered to express specialised molecules that recognise proteins on the surface of the tumour cells. These molecules target the T cells specifically to the tumours, avoiding indiscriminate damage to non-cancerous cells. The team have already identified some molecules on pancreatic cancer cells that can be successfully recognised by CAR T cells, such as avb6, and are working to identify more targets.

2) Utilising specially engineered viruses to optimise CAR T cell therapy.  These specially engineered viruses only target cancer cells and, once inside the cell, the viruses produce molecules called chemokines that attract CAR T cells to the tumour site. It is hoped that these viruses can be administered to the patient to maximise the recruitment of CAR T cells to the tumour.

3) Attacking the fibrotic, hypovascularised tumour environment. Drugs can be used to target the cells and tissue surrounding the tumour. Previous research performed by Prof Kairbaan Hodivala-Dilke and her team identified a drug that increases blood vessel production in pancreatic tumours. The team will use this drug and others to attack the tumour sites in a bid to increase accessibility for immune cells and drugs to the area.

Prof Lemoine said:

The Pancreatic Cancer UK Grand Challenge has brought together three of the BCI’s most exciting developments in biological therapy – immune cell therapy, stromal targeting and oncolytic virotherapy – to crack the problem of pancreatic cancer. It really is a huge challenge but the BCI team and our collaborators at Kings College are up for it.

The team believe that a combination of all three of these approaches is required to target pancreatic cancer effectively. The treatment will first be investigated in pre-clinical models, with the ultimate aim of translating these approaches into humans.