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!
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
14.12.2018 | Power and Electrical Engineering
14.12.2018 | Physics and Astronomy
14.12.2018 | Physics and Astronomy