Immunotherapy for Pancreatic Cancer Boosts Survival by More Than 75% in Preclinical Models
- The T cells used were engineered to recognize and kill cells bearing a protein called mesothelin, which is overproduced by virtually all pancreatic tumors.
- Animals that received T cells engineered to recognize a noncancerous protein survived on average 54 days after their cancer became detectable. Those that received the mesothelin-directed cells lived an average of 96 days, a 78% bump.
- Researchers are planning to launch a phase I clinical trial to test the therapy within the next year.
A new study in mice by researchers at Fred Hutchinson Cancer Research Center has found that a specialized type of immunotherapy—even when used without chemotherapy or radiation—can boost survival from pancreatic cancer by more than 75%. The findings are promising, and human clinical trials are planned within the next year. The study was published by Stromnes et al in Cancer Cell.
The study, led by Sunil Hingorani, MD, PhD, and Philip Greenberg, MD, both members of the Clinical Research Division at Fred Hutch, tested the immunotherapy on mice genetically engineered to grow pancreatic tumors very similar to those of human pancreatic cancer. The mouse model, developed by Dr. Hingorani, already has led to a first-in-humans clinical trial that is showing early promise in some patients with advanced pancreatic cancer.
Pancreatic cancer is notoriously difficult to treat, said Dr. Hingorani, because it recruits the body’s natural systems to construct both a tough physical barrier around tumors, as well as an immune-cloaking device that keeps other, disease-fighting immune cells from recognizing the cancer.
Unlike any other cancer, pancreatic tumors are able to survive with a significantly decreased blood supply. As a consequence, chemotherapy, commonly administered via the bloodstream, has a difficult time getting inside. The tumors not only commonly grow quite large before patients notice something is wrong, but they are very prone to metastasize.
The researchers devised a therapy using T cells that they engineered in the lab to recognize and attack pancreatic cancer.
T-cell therapy is showing promise as a treatment for several types of blood cancers, but aiming these cells at solid tumors like pancreatic cancer has historically proven more difficult, Dr. Hingorani said. Part of the challenge comes from the access to tumor cells—or lack thereof.
T-cell therapy is administered through the bloodstream, like chemotherapy. But to their surprise, the T cells—engineered to recognize and kill cells bearing a protein called mesothelin, which is overproduced by virtually all pancreatic tumors—got into the mice’s tumors and started attacking them.
In the mouse model of the disease—which is actually slightly more aggressive than the human version, Dr. Hingorani said—animals that received T cells engineered to recognize a noncancerous protein survived on average 54 days after their cancer became detectable. Those that received the mesothelin-directed cells lived an average of 96 days, a 78% bump.
Although the researchers weren’t expecting to take this first version of the T-cell therapy to clinical trials, that’s now their plan. Their team has already built the human version of the special T-cell protein that recognizes mesothelin. They’re planning to launch a phase I clinical trial to test the therapy’s safety in patients with advanced pancreatic cancer within the next year.
“As best we can tell, this would be a better therapy than anything that exists for pancreatic cancer right now,” Dr. Greenberg said. “It’s hard to be this optimistic without ever having treated a pancreatic cancer patient with this [therapy], but the biology of what we’re doing looks so remarkably true and good.”
Drs. Hingorani and Greenberg are the corresponding authors for the Cancer Cell article.
The study was funded by the National Institutes of Health, the Giles W. and Elise G. Mead Foundation, and Juno Therapeutics.