University of Southern California (USC) researchers have come up with a test vaccine that successfully prevents prostate cancer development in 90 percent of mice genetically engineered to contract the disease.
According to W. Martin Kast, a professor of Molecular Microbiology and Immunology at the USC/Norris Comprehensive Cancer Center and the Keck School of Medicine of USC, and his research colleagues, this strategy might prove beneficial for those with rising levels of PSA (prostate specific antigen), a potential diagnostic indicator of prostate cancer.
"By early vaccination, we have basically given these mice life-long protection against a disease they were destined to have. This has never been done before and, with further research, could represent a paradigm shift in the management of human prostate cancer," Kast said.
Kast said that unlike vaccines currently being tested, which offer limited clinical benefit, the new approach would specifically target the pre-cancerous state with the aim of preventing cancer from developing.
This preventive vaccine is designed to mount an immune response against prostate stem cell antigen (PSCA), the protein target of some therapeutic vaccines under development.
PSCA, a membrane protein, is over-expressed in majority of early-stage prostate cancers, but its expression shoots up in all prostate tumors as they grow and advance. PSCA is also expressed at low-levels in normal prostate gland tissue as well as in the bladder, colon, kidney and stomach.
For the study, a prime-boost vaccination scheme was created using two kinds of vaccines and was later tested on 8-week-old mice that were genetically altered to develop prostate cancer later in life.
While the first vaccine delivered a fragment of DNA that coded for PSCA, thus resulting in an invasion 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," said Kast.
At the end of the year, two of the twenty mice developed prostate cancer in the experimental group. On the other hand, all control mice died of the disease. Besides, all the mice in the experimental group had 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. The vaccination turned the cancer into a chronic, manageable disease," said Kast.
It was also discovered 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.
He added: "We feel this is a very promising approach. With just two shots, the vaccine will prime immune cells to be on the lookout for any cell that over-expresses PSCA."
The study is published in one of the recent issues of Cancer Research.