Researchers at Queen Mary University of London have identified a new therapy target, a protein called CEACAM7, that could be used to help treat pancreatic cancer.
The team managed to create a CAR T cell therapy using this target that was able to kill pancreatic cancer cells in the lab and also in a mouse model.
Pancreatic cancer affects around 57,600 adults a year in the U.S. and is difficult to diagnose and treat. It has a poor prognosis and is the fourth leading cause of cancer death with a 5-year survival rate of only 9%. Most (around 85-90%) pancreatic cancers are adenocarcinomas, such as pancreatic ductal adenocarcinoma, whereas a much smaller percentage are less aggressive, neuroendocrine tumors.
New treatments for this aggressive form of cancer are greatly in demand. John Marshall, Ph.D., a professor at Queen Mary University of London and colleagues carried out a study to investigate whether CEACAM7, a protein found to be present at high levels in pancreatic ductal adenocarcinoma tumor tissue, but not in other cells in the body, could be a good target for new therapies.
In recent years, different forms of immunotherapy have revolutionized cancer treatment. Chimeric antigen receptor (CAR) T cells are one such therapy. They are engineered, often from a patient’s own cells, to use the power of the immune system to target specific cancers. To date they have been most effective at treating ‘liquid’ blood cancers such as leukemia, but less effective at targeting more ‘solid’ tumors like breast, lung or pancreatic cancer.
One of the reasons solid tumors are harder to target is that the CAR T target proteins have to only exist in tumor cells in order to avoid toxic side effects from the therapy. Marshall and colleagues developed a CAR T cell therapy targeting CEACAM7 to assess whether it could be used to target this type of cancer, without excessive toxicity.
As described in the journal Clinical Cancer Research, Marshall and team used their CAR T cell therapy to target pancreatic cancer cells in culture in the lab and also in a mouse model. They found that it not only destroyed the cancer cells in culture, but also led to complete tumor regression in 3 of 5 mice with pancreatic cancer given the CAR T cell therapy without major toxicity problems.
“This is an exciting development. Finding that CEACAM7 allows us to kill pancreatic cancer cells specifically with CAR T cells while having no significant toxicity in non-tumor tissues, gives us hope that this strategy could be effective in the future,” says Marshall. “It is also possible that other types of immune-based therapies could be directed to CEACAM7 for the treatment of pancreatic cancer.”
CEACAM7 has not been studied in depth until now, but this early research shows that it could be a useful target for this difficult to treat cancer in the future.
Deepak Raj, Ph.D., a postdoctoral researcher at Queen Mary and first author of the study, noted that in order for a therapy to be developed to the clinical stage “it would be important to assess a larger number of antibodies against CEACAM7, not only to generate and test a larger panel of CAR T cells that may have increased efficacy against pancreatic cancer, but also to more conclusively rule whether low levels of CEACAM7 are present in normal tissues.”
