Switchable CAR-T Cells Target Pancreatic Ductal Adenocarcinoma


Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related deaths in the world, and in spite of sustained medical efforts, the incidence rate is rising.

Chimeric antigen receptor T (CAR-T) has already shown incredible success in treating hematological diseases. The procedure involves harvesting T-Cells from the patient, combining them with engineered receptors and then injecting them back to fight the cancer cells. This type of immunotherapy offers significant advantages over standard courses. It’s better targeted and safer for the patient, compared to chemotherapy or radiation.

The study sought to apply CAR-T therapy on other types of cancer, like PDAC, where results were not as impressive. The team, comprised of doctors from Australia, the U.K. and the U.S.A., realized that by introducing a Fab-based ‘switch’, they could tune the response. By combining CAR-T and the tumor antigen-specific Fab molecule, they were able to observe “complete remission in difficult-to-treat, patient-derived advanced pancreatic tumour models”.

Aiming for the HER2 (human epidermal growth factor receptor 2) gene, a known cancer marker which can upregulate tumor cells, proved a successful strategy. “Rapid tumour clearance was observed in the switchable CAR-T cells+HER2 switch and conventional HER2 CAR-T cell cohorts”. This prompted the conclusion that “data therefore confirm the efficacy of HER2 targeting in disseminated metastatic PDAC tumours via either conventional CAR-T cells or the switchable CAR-T systems.”

Pancreatic cancer often goes into metastasis because it generally offers no initial symptoms. Because of this, survival rates are fairly low, dipping below 10% for the first 5 years after diagnosis.