“By early vaccination, we have basically given these mice life-long protection against a disease they were destined to have,” said the study’s lead investigator, W. Martin Kast, Ph.D., a professor of Molecular Microbiology & Immunology and Obstetrics & Gynecology at the Norris Comprehensive Cancer Center. “This has never been done before and, with further research, could represent a paradigm shift in the management of human prostate cancer.”
Now, men with rising PSA levels but no other signs of cancer are advised “watchful waiting” – no treatment until signs of the cancer appear, Kast says. “But what if instead of a watchful wait, we vaccinate" That could change the course of the disease.”
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.
The Kast team’s 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 about one-third of early-stage prostate cancers, but expression ramps 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.
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 PSCA.”
Staci Vernick Goldberg | EurekAlert!
World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern
Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision
Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...
21.07.2017 | Event News
19.07.2017 | Event News
12.07.2017 | Event News
21.07.2017 | Earth Sciences
21.07.2017 | Power and Electrical Engineering
21.07.2017 | Physics and Astronomy