Penn study leads to new idea in treating pancreatic cancer

March 25, 2011|By Stacey Burling, Inquirer Staff Writer

Sometimes in science, what you get wrong can be just as important as what you get right.



Researchers at the University of Pennsylvania set out two years ago to prove that a new drug could marshal T cells, key players in the immune system, against pancreatic cancer. That didn't happen.

Instead, the experimental antibody turned more primitive immune-system cells that often get co-opted into helping pancreatic cancer tumors against part of the tumor structure.

Tumors shrank substantially in some patients, and median survival time lengthened by two months, to 7.4 months. That doesn't sound like much, but, with a notoriously deadly cancer, it was a step forward.




"The clinical result was far below our ultimate goal, no question," said Robert Vonderheide, senior author on the study and an associate professor at Penn's Abramson Family Cancer Research Institute. "Now we have insights that will allow us to really go forward in an accelerated way."

Usually diagnosed only after it has spread and begun causing symptoms, pancreatic cancer kills about 37,000 patients a year. Fewer than 6 percent are alive five years after diagnosis.

Treatments that harness the body's immune system are a hot area of cancer research now. Last year, Provenge, a vaccine for prostate-cancer patients, became the first FDA-approved cancer vaccine.

The Penn pancreatic-cancer study, Vonderheide said, shows that immune treatments "might be more complex and carry more possibilities than we previously thought."

In an unusual approach that Vonderheide believes will speed drug development, Penn tested the new monoclonal antibody - Pfizer's CP-870,893 - in 21 people while doing a parallel study with a similar drug in mice. The mouse study helped researchers understand what was going on in the tumors at a cellular level.

"More and more at Penn, this is a high priority," he said, referring to linked animal and human studies. "It's only been possible because the type of animal model has improved so much in the last five years."

In the study, people with pancreatic cancer were given gemcitabine, a standard chemotherapy drug, and the experimental drug, which binds and stimulates a cell surface receptor called CD40. It regulates T cell activation. The researchers thought the T cells would attack the tumor.