Switchable CAR T-Cell System Shows Promise in Pancreatic Cancer Treatment

A novel cell-based immunotherapy using a switch control approach eradicated pancreatic cancer cells in mice, including cancer cells that had already spread to the liver and lungs, according to a new study.
Pancreatic cancer is an aggressive disease with one of the lowest survival rates of all cancers, indicating a critical unmet medical need for more effective therapies. The American Cancer Society estimates that 55,440 individuals will be diagnosed with pancreatic cancer in the United States in 2018 and 44,330 will die from the disease.
Immunotherapy with chimeric antigen receptor (CAR) T-cells have represented a novel strategy for targeting and destroying cancer cells; however, its efficacy treating solid tumors is inhibited by toxic adverse effects.
The study, published in Gut, used pancreatic cancer cells from patients with late-stage disease and transplanted them into mice. The researchers used a CAR T-cell therapy approach, taking patients’ immune cells and modifying them into CAR T-cells to specifically identify and eliminate the cancer cells. However, the researchers used a novel technology that allowed them to completely control the activity of the CAR T-cells.
The technology, called a switchable CAR T system, allows the treatment to be turned on and off, or have its activity changed to a desired level, which can minimize adverse effects and improve safety, according to the researchers.  
“Our work suggests that our new ‘switchable’ CAR T-cells could be administered to human patients with pancreatic cancer, and we could control their activity at a level that kills the tumor without toxic side effects to normal tissues,” lead author Dr Deepak Raj, from Queen Mary’s Barts Cancer Institute, said in a press release.
According to the study, switchable CAR T-cells followed by administration of the switch directed against human epidermal growth factor receptor 2 (HER2) induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumor models. Additionally, the switchable CAR T-cells were found to be as effective as conventional HER2 CAR T-cells.
The results indicate that a switchable CAR T system maintains the efficacy of treating metastatic pancreatic cancer while allowing for improved safety and reducing the risk of toxicity, the researchers concluded. 
Raj D, Yang M, Rodgers D, et al. Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma. Gut. 2018. http://dx.doi.org/10.1136/gutjnl-2018-316595
New immunotherapy offers potential cure for advanced pancreatic cancer [news release]. https://www.qmul.ac.uk/media/news/2018/smd/new-immunotherapy-offers-potential-cure-for-advanced-pancreatic-cancer.html. Accessed October 15, 2018.

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