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Pancreatic cancer is one of the deadliest types of cancer, and most patients are diagnosed after the disease has spread throughout the body. The five-year survival rate for metastatic cases is around 2-3%, and the median survival is usually measured in months rather than years.
Now, a team made up of Lili Yang and Yan-Ruide Li, from the University of California, Los Angeles (UCLA), in the United States, has designed a novel immunotherapy that could offer new hope for fighting pancreatic cancer, which has historically been very resistant to treatments.
Using the new therapy, called CAR-NKT, it is possible to selectively attack pancreatic tumor cells, even in other organs after they have been affected by metastasis.
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The therapy uses modified immune cells that can be grown in large quantities from donated blood stem cells and stored ready for use. This approach offers an immediately available treatment option and at a much lower cost than current personalized cell therapies, which also require weeks of culture time that many pancreatic cancer patients simply do not have.
CAR-T cell therapies have revolutionized the treatment of certain cancers, but have struggled to combat solid tumors such as pancreatic cancer. Pancreatic tumors build a dense protective barrier of connective tissue and suppressor immune cells that prevent therapeutic cells from entering the tumor. In addition, these tumors possess a great capacity to camouflage themselves, constantly changing their molecular markers to evade detection.
To overcome these obstacles, Yang's team harnessed a rare but potent type of immune cell: invariant natural killer T cells (NKT cells). By equipping them with a chimeric antigen receptor (CAR), targeting mesothelin (a protein present in pancreatic cancer cells), these NKT cells gain the ability to identify and attack tumors through multiple independent mechanisms simultaneously.
You can With all preclinical studies now complete, the team is preparing the paperwork to begin clinical trials and verify the validity of the treatment in humans. Yang, Li, and their colleagues detail the technical aspects of their new treatment in the academic journal Proceedings of the National Academy of Sciences (PNAS), under the title “Targeting orthotopic and metastatic pancreatic cancer with allogeneic stem cell–engineered mesothelin-redirected CAR-NKT cells.”
