Apr. 20, 2007 A dendritic cell-based therapeutic vaccine for pancreatic cancer developed by researchers at the University of Pittsburgh School of Medicine has successfully stalled the disease from progressing in a handful of patients three years post-vaccination. The results, part of a press briefing on cancer vaccines held at the annual meeting of the American Association of Cancer Research in Los Angeles, provide promising evidence that the vaccine can trigger a patient's own immune system to rally against pancreatic cancer and offer new insights into how the vaccine could be made even more effective. The study is abstract number 4896 in the meeting proceedings.
"Pancreatic cancer is extremely resistant to chemotherapy and radiation and, as a result, has a very high mortality rate," said Andrew Lepisto, Ph.D., first author of the study and post-doctoral researcher, department of immunology, University of Pittsburgh School of Medicine. "One strategy to improve the odds of survival is to help the immune system recognize the presence of pancreatic cancer cells and attack them. Our study, although small, demonstrates that this strategy can be used with some success in pancreatic cancer patients by slowing down, or even stopping, the progression of cancer."
The Pitt team created a therapeutic vaccine for pancreatic cancer made up of a synthetic version of MUC1 -- a tumor-associated protein that is expressed by pancreatic tumor cells -- combined with the patient's own dendritic cells, which act as the quarterbacks of the immune system by coordinating its attack against foreign invaders.
The current study, the fourth in a series of MUC1 vaccine trials at the University of Pittsburgh School of Medicine, included 12 patients with pancreatic cancer who received the vaccine by injection once every three weeks for a total of three doses and were given a booster dose six months later. Four patients demonstrated a stable and continuous presence of antibodies against MUC1 and have no evidence of disease more than three years after the vaccination was completed and close to five years after diagnosis and surgery.
The research team also examined the specific immune response to the vaccine by sampling the blood of the patients involved in the study. They found that all the patients had an active immune response to the vaccine. They also learned the number of suppressor T cells, a special type of T cell that stifles the activation of the immune system, increased following each vaccine injection, potentially limiting the greater efficacy of the vaccine.
"As we move forward in this research, we will be looking at ways to improve the vaccine by preventing the activation of suppressor T cells," said Dr. Lepisto. "One way to do this is to use additional therapies that specifically target these cells in combination with the vaccine."
Pancreatic cancer is one of the most difficult cancers to treat because it is undetectable by a physical exam, asymptomatic and progresses quickly. Most patients die within six months of diagnosis. These factors limit the amount of data available for research, hindering significant advances in the understanding and treatment of the disease.
Co-investigators of the study and senior authors are Olivera Finn, Ph.D., leader, Immunology Program, University of Pittsburgh Cancer Institute, and professor and chair, department of immunology, University of Pittsburgh School of Medicine, and Ramesh Ramanathan, M.D., previously with the University of Pittsburgh Cancer Institute. The study was funded by grants from the Lustgarten Foundation, the National Cancer Institute and the Nathan Arenson Fund for Pancreatic Cancer Research.
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