“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!
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
New antibody analysis accelerates rational vaccine design
09.08.2018 | Scripps Research Institute
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.
Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
15.08.2018 | Physics and Astronomy
15.08.2018 | Materials Sciences
15.08.2018 | Life Sciences