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Vaccine Power: Immune cells target cancerous tissue

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10:04am, February 20, 2002
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In its first test in people, a new vaccine shows signs of fighting prostate cancer in men who have the disease. The treatment enlists a person's own immune cells to attack prostate tissue, including cancerous tissue. Despite assaulting some healthy cells, the vaccine appears safe and potentially effective in people, say scientists at Duke University Medical Center in Durham, N.C.

Researchers have been developing vaccines against cancer for several decades, but progress has been slow (SN: 6/13/98, p. 380: http://www.sciencenews.org/sn_arc98/6_13_98/bob1.htm). Anticancer vaccines differ from most other vaccines by targeting tumors instead of microbes.

The newly tested vaccine consists of immune cells called dendritic cells. Normally, these trigger a further immune response when they engulf and then display on their surfaces various proteins and other substances from bacteria, viruses, or other foreign bodies. The display signals the immune system's T cells to destroy the disease-causing elements. However, dendritic cells and the rest of the immune system typically fail to recognize cancers.

To overcome that limitation, the researchers extracted dendritic cells from the blood of men with prostate cancer. They next exposed each man's cells to genetic material that normally encodes the protein known as prostate-specific antigen (PSA), which increases steadily in men with growing prostate cancer.

The scientists injected the altered dendritic cells back into the patient.

They hoped that the treated cells would display PSA and thus trigger T cells to attack prostate and tumor cells.

Over 6 weeks, the scientists gave three doses of the personalized vaccine to each of 13 men with prostate cancer. In all the men, the researchers measured a dramatic rise in the number of T cells capable of responding to PSA, suggesting that the vaccine had sparked the desired response.

In six of the seven patients given further tests, the rate of increase of PSA circulating in the blood slowed down after the vaccinations. The change may indicate that tumor growth was arrested in the patients. The treatment caused only a few minor side effects, says Johannes Vieweg of Duke.

The team reports its findings in the Feb. 1 Journal of Clinical Investigation.

"This study is a big step forward," says Rong-Fu Wang at the Baylor College of Medicine in Houston. The technique could also have tremendous potential if applied to other cancers, he says. That will be trickier than it is for prostate cancer, Wang cautions, because these dendritic cells flagged all prostate cells for immune attack. "The prostate is nonessential," Wang points out, but the same isn't true of lung tissue, for example.

Vieweg says that because of the small number of patients in the current study, the anticancer results aren't conclusive, but proving that the procedure is safe and feasible paves the way for a much larger study. "Now, we can unleash the brakes on testing" of self-immunization therapies that treat immune cells with genetic material, he adds.

With his colleagues at Baylor, Wang reports in the February Nature Biotechnology a promising new way to get dendritic cells to flag tumors for T-cell attack. In many anticancer vaccines, the clinical response hasn't been dramatic, says Wang. The researchers hypothesized that the problem might be that dendritic cells simply have trouble engulfing and retaining parts of cancerous cells.

The researchers devised a possible solution to this problem by using molecules called cell-penetrating peptides. The peptides are readily taken up by cells, and they drag along material ranging from tiny protein fragments to massive molecules.

Wang's team attached cell-penetrating peptides to molecules from cells of a skin cancer known as melanoma. The researchers found that dendritic cells in mice engulf the combination and hold onto it for longer periods than they do with the melanoma molecules alone. Wang says he hopes to use the cell-penetrating peptides to "significantly improve the clinical response to cancer vaccines."

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