The work was done on mice, so the researchers caution that clinical use could be several years away. But the finding, reported in the advance online edition of the December issue of Nature Medicine, is lauded as groundbreaking by a prominent researcher in the field.
Ralph A. Reisfeld, a professor of immunology at The Scripps Research Institute in California, and his team first targeted a protein produced in new blood vessels, called vascular endothelial growth factor receptor 2, or VEGF receptor 2. This protein is one of several "activators" of new blood vessel growth, a process called angiogenesis. New blood vessel growth is critical, experts now agree, for cancerous tumors to grow and spread.
The researchers gave the animals genetically engineered bacteria that also contained a gene to express the VEGF receptor 2 protein. When the immune system activated to fight off the mild infection from the bacteria, it also killed the protein that spurs new blood vessel growth to the tumors. The vaccine worked against melanoma, colon cancer and lung cancer in the animals.
"The immune response triggered by the vaccine destroys the blood vessels that nourish the tumor," says Dr. Andreas G. Niethammer, a co-author on the paper who is also at Scripps Research Institute. The other authors are from the La Jolla Institute for Molecular Medicine in San Diego and the Universitaets-Hautklinik in Wuerzburg, Germany.
The concept of giving a DNA vaccine with weakened bacteria is not new, Reisfeld says. "The new thing is, we have killer cells attacking the blood vessels within the tumor." The killer cells, the researchers also found, have a very good memory.
"The mice were vaccinated and allowed to sit for 10 months (a lengthy period in a mouse's lifespan), and then they were challenged with tumor cells. They dramatically suppressed the growth of these tumor cells," Reisfeld adds.
The animals did have a delay in wound healing as a side effect, the researchers report, but there was no effect on the mice's fertility or neuromuscular performance.
Most DNA vaccines under study now are designed to attack the tumor directly, not the blood supply to it, Reisfeld and Niethammer say.
The problem with that approach is that tumor cells are constantly mutating, says Dr. Judah Folkman, a professor of surgery and cell biology at Harvard Medical School and Children's Hospital in Boston and a pioneer in angiogenesis research.
He lauds the new research as "breaking new ground," particularly since the killer cells have a memory. "They've changed the target," he says, from the tumor to the endothelial cells that line the blood vessels and promote new blood vessel growth. "They are targeting the supply line," he notes.
Another plus of the new vaccine, Folkman says, is that it can be administered orally, rather than intravenously as most other immunotherapy cancer treatments are given.
"It looks promising as far as a potential treatment," agrees Dr. Mai. N. Brooks, an associate professor of surgical oncology at the UCLA David Geffen School of Medicine who was formerly a researcher in Folkman's laboratory.
"There is a long road between what works for mice and what works for men and women," she adds. "But this seems to be a unique approach to anti-angiogenesis. The idea of a vaccine that will confer long-lasting immunity is beautiful."
"We let the body do most of the work," Reisfeld explains. Eventually, the hope is that such a vaccine would work against a variety of cancers, he says. However, the vaccine must still be tested for toxicity and undergo clinical trials in humans. Reisfeld estimates it will take at least four to seven years before the vaccine might be routinely available.
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