The study findings also represent a new way to think about the use of therapeutic prostate cancer vaccines, Kast says. Vaccines now in testing are designed to treat men whose cancers are advanced and unresponsive to therapy, and results have offered limited clinical benefit, he says. This novel approach targets the precancerous state with the aim of preventing cancer from developing, he says.
Designed preventive vaccine van Kast van The team is to mount an immune response against prostate stem cell antigen (PSCA). the protein target of some in ontwikkeling therapeutic vaccines. PSCA, a membrane protein, is over-expressed in about one - third of early-stage prostate cancers, but expression ramps up in all prostate tumors as they grow and advance. Is also PSCA expressed at low-levels in normal kidney. colon. van prostaat tissue as well as in the bladder and stomach.
The researchers created a prime-boost vaccination scheme using two kinds of vaccines and tested it in 8week-old mice that were genetically altered to develop prostate cancer later in life. Vaccine van The first delivered a simply fragment of DNA that coded for PSCA. thus producing an influx of protein to alert the immuunsysteem PSCA. The booster shot, given two weeks later, used a modified horse virus to deliver the PSCA gene.
„Confronting the different ways forces it to mount a strong response.“ Kast van immuunsysteem in two said.
In the experimental group, two of 20 mice developed prostate cancer at the end of one year, and by contrast, all control mice had died of the disease. Researchers found that mice in the experimental group had all developed very small tumors that did not progress. Were surrounded tiny nodules „There of prostate cancer in the mice that were by an army ofimmuunsysteem cells.“ Kast said. "The vaccination turned the cancer into a chronic, manageable disease."
The vaccination strategy also works with other antigens, Kast says. The researchers recently tried another prostate cancer membrane target and found that after 1.5 years, 65 percent of experimental mice were still alive, and of those that died, the suspected cause was old age.
Crucially, investigators further found that treated mice did not develop autoimmune disease, a side effect that could develop if the vaccine had also targeted PSCA expression in normal cells. "Theoretically, the vaccine could produce a response in any tissue that expresses the antigen, but the fact that PSCA is expressed in such low levels in normal tissue may prevent that complication," he said.
Still, studies in humans are needed to ensure autoimmunity does not develop, Kast says.
"We feel this is a very promising approach," he said. "With just two shots, the vaccine will prime immune cells to be on the lookout for any cell that over-expresses PSCA."
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The study was funded by a pre-doctoral training grant from the National Institutes of Health and a grant from the Margaret E. Early Medical Research Trust. Co-authors include researchers from the University of Southern California as well as from AlphaVax, inc., of Research Triangle Park, North Carolina.
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