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Stem cell therapy for pancreatic cancer

Recipient: Dr Ralf Zwacka

Host Institution:  University of Essex

Title: Stem cell therapy for pancreatic cancer

Type of award: 2016 Research Innovation Fund

Funding: £74,280

Pancreatic cancer is incredibly complex, involving multiple different cell types. Many tumours are resistant to treatment by chemo- and radiotherapy and these treatments often come with severe, unwanted side effects. We still do not know enough about pancreatic cancer progression and resistance to therapy to understand why the disease does not respond well to the cancer drugs that are available – or to support the development of new cancer drugs or treatment approaches.

Patients with pancreatic cancer therefore desperately need new approaches to finding pancreatic cancer treatments that improve survival rates and outcomes.There has been growing interest in the field of immunotherapy as a new treatment for pancreatic cancer, having seen significant promise in other diseases such as blood cancers.

Immunotherapy works by harnessing the power of the body’s own immune system and using it to fight against cancer cells. Researchers can also artificially modify the immune cells so that they can specifically identify, attack and eliminate cancer cells.Unfortunately, solid cancers (such as pancreatic cancer) cannot be as easily fought using this approach. We now need to understand more about the ways that solid cancer cells are resistant to immunotherapy treatments.

In this project, Dr Zwacka will be developing a new approach to immunotherapy, using engineered stem cells to re-activate the immune system so that it starts recognising and fighting pancreatic cancer cells.On the surface of cancer cells is a protein called PD-L1. This protein binds with another protein, PD-1, which is found on T cells, an important part of our immune system. This interaction prevents our immune system from recognising the cancer cells and fighting against them.Researchers have developed molecules that bind themselves to the protein PD-L1, preventing the interaction with the T cells and allowing the immune system to take up the fight against the cancer cells. These molecules have so far not been effective for pancreatic cancer as there is another cell type involved which puts up a barrier preventing them from working. These are called cancer associated fibroblasts.In this project, Dr Zwacka will be testing cells that are very similar to cancer associated fibroblasts that will be able to break through the barrier they put up. By loading these cells with PD-1 protein, they will be able to deliver this directly to the cancer cells, and therefore stop the interactions with the protein on the T cells. This then frees up the T cells, allowing the immune system to do its job and hunt out and tackle the cancer cells.

Pancreatic cancer is the fourth leading cause of cancer-related deaths. Current treatment options for this disease are limited, and most patients diagnosed with this disease have a poor prognosis. New approaches to pancreatic cancer treatment are therefore urgently needed. This is an extremely promising area of investigation and based on the results this could lead to a ground-breaking new clinical trial to test a new immunotherapy treatment for people with pancreatic cancer.