Antibody Attack on Pancreatic Cancer

A new therapy for pancreatic cancer reduced the growth rate of tumors in patients in a pilot trial and, in a separate study, kept mouse tumors at bay altogether. The treatment, reported in today's issue of the Proceedings of the National Academy of Sciences, rallies the immune system's "killer" cells to fight the devastating cancer.

Fewer than 1% of pancreatic cancer patients live more than 5 years after diagnosis. "There is no successful medical treatment," says Wolff Schmiegel, a gastroenterologist at Ruhr University in Bochum, Germany. Hoping to improve this grim statistic, Schmiegel's group set out to exploit the immune system's ability to recognize some cancer cells as enemies by the telltale mat of proteins, such as epidermal growth factor receptors (EGFRs), that stud their surfaces. A cancer cell with lots of EGFRs draws a lot of antibodies that latch onto the receptors; the antibodies, in turn, attract killer cells that destroy the tumor cell. Increasing the number of receptors on tumor cells, the researchers reasoned, would boost the effectiveness of so-called immunotherapy, in which engineered antibodies are administered to attract the killer cells.

Four years ago, Schmiegel and his colleagues found they could raise EGFR levels on the surface of pancreatic cancer cells by adding a protein called tumor necrosis factor-a (TNF-a) to cultured cells. In their latest work, the researchers injected human pancreatic cancer cells into mice, which soon developed tumors. Treating these mice with TNF-a and EGFR antibodies kept the tumors from growing larger, as those of control mice swelled eightfold.

In a second study, Schmiegel's team treated 26 patients at similar stages of pancreatic cancer with TNF-a and a varying amount of the antibody. The tumors of patients receiving the most antibodies grew by less than 10% on average, while those in patients receiving the lowest dose more than doubled in size. The high-dose patients also lived more than twice as long on average as those on the lower dose, but that result was less reliable, because of the small number of patients.

The therapy offers a ray of hope for pancreatic cancer patients, says immunologist Hilary Koprowski of Thomas Jefferson University in Philadelphia, who says he is "cautiously optimistic" that the treatment will prove successful in the long term. "I wish there were more difference in survival rates" between the lower and higher dose groups, he says. Schmiegel is now working toward the next step--a study with more patients that could give more trustworthy information on survival times.