Researchers from the Mayo Clinic, University of South Florida, and University of Torino employed substances called toll-like receptor agonists to help a synthetic peptide vaccine raise the immune system response against breast cancer tumors. Simultaneously, they used antibodies to blunt other aspects of the immune system that might interfere with a strong killer T cell response, improving the effectiveness of the vaccine.
In the February 1 issue of Cancer Research, the researchers report that their strategy was effective in preventing spontaneous tumors in transgenic mouse models for breast cancer, even when the vaccine was given when the mice already had early stage cancer.
"The challenge is to get a foreign peptide recognized by the immune system as a threat so it can react and produce anti-tumor immune cells," said Esteban Celis, M.D., Ph.D., professor in the department of interdisciplinary oncology at the H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida in Tampa. "We've shown that stimulating the immune system using toll-like receptor agonists is very important to alerting it and producing lymphocytes that will have an anti-tumor effect."
According to Celis, the immune system usually doesn't react as strongly to a synthetic peptide in a vaccine as it does against an infectious agent, which is why immune system boosters such as toll-like receptor agonists, which mimic bacterial DNA, help. They also used anti-CD25 antibodies to tie up immune system T regulatory cells, which often serve as brakes that can reduce responses to the vaccine.
The researchers studied both normal mice and transgenic mice carrying an activated HER2/neu oncogene, which has been linked to breast cancer in humans. In order to get a protective immune response, the transgenic mice were repeatedly given vaccine in combination with the toll-like receptor agonist or were given antibodies that blocked their protective T regulatory cells. Celis and his colleagues found that the peptide vaccine administered this way could prevent or slow the growth of injected tumor cells, and showed some benefit against early stage spontaneous breast tumors.
The vaccine was most effective in preventing spontaneous tumors when it was given once at week eight – along with anti-CD25 antibodies -- when most mice have excessive and often precancerous breast tissue growth called hyperplasia. It completely prevented spontaneous tumors in HER2/neu mice up to 35 weeks of age. Even without the antibody, tumors took much longer to develop, and when they did, they grew more slowly.
"This kind of therapy could be applied to women who have a high likelihood of developing cancer -- women with pre-malignant hyperplasia or who have a genetic predisposition or make-up that makes them at high risk," Celis said.
Although the peptide vaccine was effective in preventing spontaneous tumors in the HER2/neu mice, Celis cautions that the mice had to be vaccinated prior to the appearance of measurable tumors and that the animals had to receive repeated immunizations.
"Once tumors appear, only certain mice respond and there is only a delay in tumor growth," he said. "It extends survival but does not cure the mice. We know that the immune response in these mice is much lower than in the animals that are younger, and it's likely that the tumor is making something that is inhibiting the immune response."
Greg Lester | EurekAlert!
How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Life Sciences
18.01.2017 | Health and Medicine
17.01.2017 | Earth Sciences