Pancreatic cancer, which affects about 60,000 Americans every year, is one of the deadliest forms of cancer. After diagnosis, fewer than 10 percent of patients survive for five years.
While some chemotherapies are initially effective, pancreatic tumors often become resistant to them. The disease has also proven difficult to treat with newer approaches such as immunotherapy.
In a new study from MIT, researchers have developed an immunotherapy strategy and shown that it may eliminate pancreatic tumors.
The new therapy, which is a combination of three drugs that help boost the body’s own immune defenses against tumors, is expected to enter clinical trials later this year.
The body’s immune system contains T cells that can recognize and destroy cells that express cancerous proteins, but most tumors create a highly immunosuppressive environment that disables these T cells, helping the tumor to survive.
Immune checkpoint therapy (the most common form of immunotherapy currently being used clinically) works by removing the brakes on these T cells, rejuvenating them so they can destroy tumors.
But pancreatic tumors don’t express as many cancerous proteins, known as neoantigens. This would give T cells fewer targets to attack.
In the study, the team found that many pancreatic tumors do in fact express cancer-specific neoantigens.
Using mice of pancreatic cancer, the researchers tested a variety of combinations of experimental drugs.
They found that combining three cancer drugs (CD40 agonist antibodies with both a PD-1 inhibitor and a TIGIT inhibitor) could lead to a dramatic effect.
Pancreatic tumors shrank in about half of the animals given this treatment, and in 25% of the mice, the tumors disappeared completely. Furthermore, the tumors did not regrow after the treatment was stopped.
None of these drugs are FDA-approved yet, but they have each reached phase 2 clinical trials. A clinical trial on the triple combination is expected to begin later this year.
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The study is published in Cancer Cell. One author of the study is William Freed-Pastor.
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