The researchers created a prime-boost vaccination scheme using two kinds of vaccines and tested it in 8-week-old mice that were genetically altered to develop prostate cancer later in life. The first vaccine simply delivered a fragment of DNA that coded for PSCA, thus producing an influx of PSCA protein to alert the immune system. The booster shot, given two weeks later, used a modified horse virus to deliver the PSCA gene.
Confronting the immune system in two different ways forces it to mount a strong response, Kast 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. There were tiny nodules of prostate cancer in the mice that were surrounded by an army of immune system 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
|Contact: Staci Vernick Goldberg|
American Association for Cancer Research