Go. pancreatic tumor that had spread to the liver ( left ) disappeared after the patient has received chemotherapy and an antibody that stimulates macrophages ( right ).
G. Beatty et al., Science, 331 (25 March 2011)
Pancreatic cancer is relentless and usually kills patients within a few months. Now, scientists report that a treatment that ignites certain immune cells extends the life of pancreatic cancer patients by more than 30%. Although beneficiaries survived only an additional 2 months, cancer researchers are enthusiastic about the results.
The statistics on pancreatic cancer are dismal. Only about 5% of patients with ductal pancreatic adenocarcinoma (PDA), the most common form of the disease, are alive 5 years after diagnosis. And chances of defeating pancreatic cancer have not improved much over the past 35 years, noted surgeon and cancer researcher Jason Fleming MD Anderson Cancer Center in Houston, Texas. "We're really at square one with survival," he said.
A dirty tricks pancreatic cancer involves co-opting of white blood cells called leukocytes. Instead of attacking these defectors seeping cancer and "essentially wall it off the antitumor effects of the immune system," said Robert Vonderheide tumor immunologist at the University of Pennsylvania Abramson cancer Center. Vonderheide and his colleagues wondered if they could turn the immune system against cancer by triggering CD40, a receptor protein carried by several types of defensive cells. Activation of CD40 is usually necessary for immune cells to take on tumors.
the researchers received doses of 21 patients with PDA gemcitabine standard chemotherapy drug and an antibody that folds on CD40. Computed tomography showed that pancreatic tumors decreased or stabilized in 15 subjects. In some recipients, the treatment also decreased the metastatic tumors, or origin of cancer colonies which have germinated in other body parts. Historically, patients receiving gemcitabine survive the PDA about 5.7 months. But as the researchers report online today in Science , patients in the experimental group lived for 7.4 months.
To determine how the treatment affected the growth of the tumor, the researchers tested genetically engineered mice that develop PDA. The combination of gemcitabine and a version of rodent and antibodies, even the activation of the CD40 single mouse tumors reduced to about 30% of the animals. The researchers expected that the activation of CD40 cause against an attack by immune cells called T cells, but to their surprise, they found that the antibody worked even in mice that lack these cells. Instead, the attackers were macrophages, a more general kind of defense cell whose jobs include munching bacterial invaders and helping to heal damaged tissue. Macrophages could wriggle through the blockade white blood cells and begin to kill tumor cells.
"These are promising results to be expanded and tested further in larger studies," said Vonderheide. A question to investigate, he said, is whether other treatment combinations increase the power to kill the activator, as pairing with a vaccine that induces T-cells to attack the tumor.
Cancer experts are impressed. "It is a great item," says Fleming. "It is certainly a big step forward," says cancer biologist Dafna Bar-Sagi of the New York University School of Medicine in New York. Stretching survival in less than two months may not seem like a big deal, but given the poor prognosis for most patients, "these numbers are important," says molecular biologist Jonathan Brody Thomas Jefferson University in Philadelphia, Pennsylvania. The three researchers who are not involved in the study, agreed that the findings highlight the importance of designing treatments that focus not only on tumor cells, but also on the neighboring tissue that helps them survive and to develop. "We need to target these cells," says Brody.
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