Cancer vaccine promising

Early trial by Hopkins researchers greatly boosts survival of pancreatic patients

November 21, 2005|By DAVID KOHN | DAVID KOHN,SUN REPORTER

Dr. Elizabeth Jaffee gets six or seven e-mails a day from desperate cancer patients and family members, pleading for help or for a spot in one of her studies.

The Johns Hopkins University researcher keeps two of these entreaties tacked to a wall in her office. One is from a 13-year-old Alaska boy whose father was dying of pancreatic cancer. The boy begs Jaffee for help: "You have to save my dad. He's my best friend."

The other is from a 16-year-old Kansas girl who had already lost her mother to breast cancer. Now her grandmother has pancreatic cancer -- if she dies, too, the girl writes, there will be no one to help pick out a prom dress.

In both cases, the cancer had progressed too far, and the patients weren't eligible for Jaffee's trials.

"You just sit there and look at them," Jaffee said of the notes. "It keeps you going."

For the past 16 years, Jaffee has been developing a vaccine for pancreatic cancer. Last week, she and her colleague, Dr. Dan Laheru, announced some good news: Their vaccine significantly improved survival rates in a small group of patients.

The results were released at a joint meeting in Philadelphia of the American Association for Cancer Research, the National Cancer Institute and the European Organization for Research and Treatment of Cancer.

"If these results hold up, it's better than anyone's done before," said Laheru, 37, an oncologist at Hopkins' Sidney Kimmel Comprehensive Cancer Center. "It's extremely exciting."

Jaffee, 45, began working on pancreatic cancer in part because it is so difficult to treat. The disease is extremely lethal: 30,000 Americans are diagnosed annually, and almost all die within a year. Although it is the 10th-most-common cancer, it is the fourth-deadliest.

Patients commonly don't notice any symptoms until too late. "It can come on very silently," Laheru says. "By the time they get diagnosed, the cancer has spread."

The road to their recent success has been long and winding. Jaffee began her work in 1989, injecting laboratory mice with thousands of different molecules, trying to discover which might help the immune system recognize and attack cancer cells.

Normally, these malignant cells can avoid detection by the immune system -- a key reason that cancer can grow and spread in the body.

After several years, she and some colleagues came across a protein called granulocyte-macrophage colony stimulating factor, or GM-CSF, which seemed to direct immune cells to cancers.

Jaffee, who is an oncologist and an immunologist at the Kimmel center, realized that inserting the protein into cancer cells could allow the immune system to recognize the enemy and initiate an attack. So she set about making a treatment vaccine to do that.

By the mid-1990s, she had devised a way to incorporate the gene that makes GM-CSF into pancreatic cancer cells. To make the resulting cells safe for medical use, she irradiated them, destroying their ability to divide and grow.

In tests on mice, the vaccine worked.

Unlike preventive vaccines, which stimulate the immune system in order to prevent a disease, Jaffee and Laheru's therapy is a treatment vaccine, designed to trigger a response to an illness in the body.

"The vaccine acts as a lure to attract immune cells to the site of the cancer," Laheru says. After being drawn to the genetically engineered pancreas cancer cells, immune cells can attack any pancreatic cancer cell, even those that don't contain GM-CSF.

But a treatment that consists of genetically engineered cancer cells makes regulators nervous. So, over the past decade, Jaffee has had to convince government and institutional authorities that the approach is safe in humans.

The effort added years to the process, she says. She keeps a photo of herself standing next to a stack of paperwork from just one of the studies: The pile is almost as tall as the 5-foot, 4-inch researcher.

In 1997 she began her first human study, of 14 patients with pancreatic cancer. The therapy showed promise; three subjects are still alive and free of cancer, a remarkable result given the disease's deadliness.

In 1999, Laheru signed on as a research fellow, and three years ago they began the most recent trial. The pair studied 60 pancreatic cancer patients, all of whom had undergone surgery to remove their tumors.

After surgery, the patients received chemotherapy and radiation treatment, as well as regular injections of a pancreatic cancer vaccine containing GM-CSF.

After one year, 88 percent of those who received the vaccine were still alive; after two years, 76 percent had survived. In general, 60 percent of pancreatic cancer patients who have had surgery live for a year; fewer than half are alive after two.

"Eighty-eight percent survival after one year -- that's impressive," says Len Lichtenfeld, deputy chief medical officer at the American Cancer Society.

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