Immunotherapy of pancreatic cancer using chimeric antigen receptor engrafted T-cells targeted against the avBeta6 integrin
Recipient: Dr John Maher
Host Institution: King's College London
Title: Immunotherapy of pancreatic cancer using chimeric antigen receptor engrafted T-cells targeted against the avBeta6 integrin
Type of award: 2013 Research Innovation Fund
Immunotherapy targets the patients' immune system against their own cancer. We propose to isolate white blood cells called T-cells and genetically modify them with a harmless virus so that they make a new protein called a chimeric antigen receptor (CAR), which is a "designer" protein made from several naturally occurring components. The CAR straddles the surface of the T-cell, with a portion that lies inside the T-cell itself and a second portion that protrudes outside, which is designed so that it binds tightly onto a "target" that is found on cancer cells, but not healthy cells. When this binding takes place, the inner part of the CAR instructs the T-cell that it should attack as it does naturally when T-cells fight infection. By using a CAR, we can harness this natural protective mechanism to attack and kill cancer cells, as has recently been achieved with patients with terminal blood cancers. This paves the way for testing of this therapy against diseases such as pancreatic cancer. In this project, we will use a CAR that binds to a target called αvβ6, which has been found in all pancreatic cancers but is rarely found in healthy tissue, and investigate whether it can cause the shrinkage of experimental pancreatic tumours.