Development of an innovative personalised CAR-NK cell therapy for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the third deadliest cancer worldwide with an increasing incidence. The 5-year survival of 7% has barely changed in 50 years and is stated as the worst of any cancer type. The immunosuppressive tumour microenvironment is believed to be the major confounding factor involved in failure of current therapies. Because of the high medical need, we will investigate the potential of a novel personalised and modified chimeric antigen receptor (CAR)-natural killer (NK) cell therapy combined with an innovative immune-priming agent. More specifically, we will first modify NK cells using the revolutionary CRISPR-Cas9 technology to make them insensitive to transforming growth factor beta-mediated immunosuppression in the tumour microenvironment. Next, these ameliorated NK cells will be modified to target both the tumour and the surrounding tumour microenvironment using different CAR constructs. Additionally, to invigorate our CAR-NK cell therapy, we will combine this with an immunostimulatory agent. This not only has the capacity to broadly activate the immune system but can also induce a greater attraction of our CAR-NK cells into the tumour to make our CAR-NK cell therapy more efficient. Hence, supported by our encouraging preliminary data, we are convinced that this project has great potential to finally overcome the crucial hurdles that block the advancement of treatment options for PDAC patients.

Keywords:PANCREAS, CELL THERAPY, CANCER IMMUNOTHERAPY

Disciplines:Cancer therapy