Triple Immunotherapy Combination Treatment for Pancreatic Cancer
Treatment for pancreatic cancer so far still focuses on immunotherapy. Recent research found a combination of three immunotherapies for cancer.
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All cancers are deadly, and one that is rarely felt in its early stages is pancreatic cancer. The good news is that researchers at The University of Texas MD Anderson Cancer Center have discovered a new immunotherapy combination for the treatment of pancreatic cancer by targeting checkpoints in T cells and myeloid suppressor cells and successfully reprogrammed the tumour immune microenvironment (TIME) and significantly improved the response anti-tumour in preclinical models of pancreatic cancer.
The results of this research were published on December 30, 2022, in Nature Cancer. The researchers used comprehensive immune profiling in mouse and human pancreatic cancer to systematically identify mechanisms of immunotherapy resistance and investigate potential therapeutic targets.
The results found that neutralizing several different immunosuppressive mechanisms of TIME could dramatically improve survival rates in laboratory models. This suggests a potential treatment option for this notoriously lethal and unresponsive cancer.
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This triple combination therapy produced a curative response unprecedented in other research models, as reviewed by Ronald DePinho, M.D., professor of Cancer Biology. The prevailing view has been that pancreatic cancer is resistant to immunotherapy. Still, this preclinical research shows that it is susceptible to appropriate combination therapy.
Pancreatic cancer is one of the leading causes of cancer deaths in the United States and other developed countries, in part because 80% of cases are diagnosed at an advanced stage. Pancreatic cancer is also considered “non-immunogenic,” meaning it is unresponsive to commonly used anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors.
In antibody testing, the researchers observed that models treated with a 41BB agonist and a LAG3 antagonist in combination with the studied cells had slower tumour progression, higher levels of indicators of anti-tumour immunity, and significantly increased survival rates compared with treatment with antibodies alone or with others.
The researchers also confirmed that both of these therapeutic targets were present in human pancreatic cancer samples, with 81% and 93% of patients analyzed having T cells with 41BB and LAG3 expression, respectively.
It was this triple combination that resulted in complete tumour regression and improved overall survival in 90% of preclinical models. In a more stringent lab model that developed multiple spontaneously occurring tumours with higher treatment resistance, the combination achieved complete tumour regression in more than 20% of cases.
These are encouraging results, especially considering the lack of effective immunotherapy options for pancreatic cancer. By targeting several synergistic mechanisms that block the immune response, researchers can give T cells a chance to fight these tumours.
Researchers are optimistic that pancreatic cancer and other non-immunogenic cancers may eventually be made susceptible to combination immunotherapy.
