Thanks to Penn, the war on pancreatic cancer has met its newest ally — the immune system.
Penn researchers are making headway on curing a disease that kills more than 36,000 people a year in the United States with a new treatment method that turns the immune system on pancreatic cancer, allowing it to attack the tumor.
A large difficulty when treating pancreatic cancer is the disease’s ability to suppress the immune system, according to Hematology and Oncology professor Robert Vonderheide, the senior author of the study.
“So the approach that we’ve used is to target the immune system and change it so that it will attack the cancer,” added instructor of Hematology and Oncology Gregory Beatty, who led the clinical trial.
Twenty five percent of the patients given the treatment had their tumors shrink by at least 30 percent and their survival time lengthened, although all eventually died.
A unique aspect of the study, however, was that while the patients were being administered the experimental treatment, mouse-models were undergoing similar trials.
Unlike mice that had previously been used to test this treatment, these mice more closely paralleled human conditions because their tumors developed gradually instead of being implanted in their mature stage on the side of the mouse. This realistic model allowed the researchers to understand what was happening to the patients on a molecular level.
“The larger study was to show that is was relevant and important for patients, but then we came back to the laboratory to understand how it was working,” said Vonderheide on the unique clinical and laboratory aspect of the study.
To start, 21 patients were given a standard chemotherapy drug — gemcitabine — in addition to an experimental antibody manufactured by pharmaceutical company Pfizer.
The idea was that the Pfizer antibody would bind with CD40, a molecule found on the surface of many different types of cells. CD40 would then activate T-cells, which would in turn attack the tumor and kill it.
However, despite the fact that the tumors shrank, the researchers realized that the T-cells actually had no role in attacking the tumor as expected. Instead, they noticed that macrophages, cells that usually helps protect the tumor, were heavily prevalent and attacking the tumor.
To understand what was happening, the researchers turned to the mouse models.
“Our study is showing that you can change the phenotype of these macrophages and actually make them now attack the cancer,” Beatty said. “It’s a ying-yang thing. Sometimes they are on the black side and they are dark. And then sometimes they are on the white side of the ying-yang.”
The researchers believe that this different approach of targeting macrophages may have implications for treating other types of cancer as well. Currently they are using the antibody in a clinical study for patients with metastatic melanoma.
