March 12, 2002
The development of a cancer vaccine is the goal and hope of cancer researchers everywhere. The idea is to load dendritic cells with cancer antigens and introduce them into the body. Dendritic cells are key players in the body's defense against cancer, because they "turn on" t-cells that kill tumors.
But in an article that appeared in Nature Medicine in December, Tulane researchers presented evidence that this approach is unlikely to work, at least not in its current formulation. On the other hand, drugs that are in development for other uses may also be effective with cancer.
"We looked in the tumors of patients with ovarian cancer for different types of dendritic cells, because nobody's ever looked inside a tumor to see what's actually there," explained Tyler Curiel, associate professor of medicine. "In the past researchers have simply taken blood from patients and studied what's circulating in their blood, but they haven't looked inside the tumor."
Curiel and his colleagues found that the two types of dendritic cells most commonly used in vaccine research were not present in the tumor. But they found many of the dendritic cells called DC2s. "They're not supposed to be there," Curiel said.
DC2s are important in making immune responses against virus infections and are very good at activating t-cells in the blood. But the DC2s in the tumor didn't behave like the DC2s in blood. Instead of turning immunity on, they were turning it off. Curiel and his colleagues were able to show that the tumor attracted the DC2 cells, protected them in the harsh tumor environment, then reprogrammed them to turn off their immune defense.
"It was very unexpected," he said. "We've identified the molecules the tumor makes to attract and protect these cells, and we think these molecules are the ones that are doing the reprogramming."
Curiel says this predicts that the tumor will be able to turn off the immunity offered by a vaccine. On the other hand, he found that if you can get DC1 cell--another kind of dendritic cell--into the tumor, it creates an effective immune response. The problem is that the tumor has "figured out" how to keep DC1 cells out.
"What we're thinking about now is an entirely new way to treat cancer," he said. "Instead of making cells outside the body, putting tumor pieces on them, and using them as a vaccine, we think you can go into the body and manipulate where cells go. We have drugs that attract DC1s. We have drugs that keep DC2s out."
Drugs that prevent DC2 from getting into tumors are already in trials as AIDS drugs--the receptors that the AIDS virus exploits are the same ones that the cancer does. "That's probably just a bizarre coincidence. But because of that people have developed a whole library of drugs that block this receptor," Curiel said.
Other drugs that induce DC1s to migrate to tumors have already been licensed for use in humans. Curiel plans to begin trials of the drugs in women with ovarian cancer this year. Curiel came to Tulane last summer from the Baylor Institute for Immunology Research in Dallas. He brought with him the core members of his team, including Weiping Zou, assistant professor of medicine, who was the first author of the Nature Medicine article.
Curiel was attracted to Tulane because of the school's commitment to growing its research endeavor. "Tulane's on the upswing, and I hope my group can add to that," he said. "I'm interested in building programs and taking things to the next level."
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