Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Strengthening the immune system's fight against brain cancer

19.03.2015

NIH-funded research suggests novel way to improve vaccine efficacy in brain tumors

When cancer strikes, it may be possible for patients to fight back with their own defenses, using a strategy known as immunotherapy. According to a new study published in Nature, researchers have found a way to enhance the effects of this therapeutic approach in glioblastoma, a deadly type of brain cancer, and possibly improve patient outcomes.


This is an artist's representation of the surface of a human dendritic cell.

Credit: Image courtesy of the National Cancer Institute.

The research was funded by the National Institute of Neurological Disorders and Stroke (NINDS) as well as the National Cancer Institute (NCI), which are part of the National Institutes of Health.

"The promise of dendritic cell-based therapy and other immunotherapies for brain cancer has been upheld for some time, but an important implication of this work is a demonstrated capacity to significantly improve the clinical impact of immunotherapy for patients with this very difficult disease," said Duane A. Mitchell, M.D., Ph.D., director of the Brain Tumor Immunotherapy Program at the University of Florida in Gainesville and co-lead author of the study.

Dendritic cells are specialized immune cells that normally capture microorganisms, and then migrate to the lymph nodes to prepare other immune players, such as T cells, to fight off the invaders.

Dendritic cells have been used for immunotherapy to target a variety of tumor types, including those that affect the brain. These cells are taken from the patient, engineered to express antigens from the tumor¬ to create a vaccine, and then injected back into the patient. Once in the patient, the engineered dendritic cells activate T cells, which can fight the tumor and also prevent it from coming back, via an immune memory response.

Dr. Mitchell and his colleagues wanted to know if increasing dendritic cell migration to lymph nodes would improve the effects of the vaccine. To test this idea, a group of glioblastoma patients was randomized to receive a tetanus booster shot before getting the tumor-antigen expressing dendritic cell vaccine.

The booster was designed to set off an inflammatory response at the site of the vaccination, prepping the immune system for a larger battle. The other group of patients were injected with their own native dendritic cells instead of a tetanus shot, and then treated with the tumor-antigen expressing dendritic cell vaccine. Both sets of patients were treated with the vaccine which was being tested for effectiveness against glioblastoma.

The vaccine used in this study was targeted against cytomegalovirus (CMV). Studies have shown that CMV is found in glioblastoma tumors, but it is unclear if the virus causes tumors or contributes to disease progression. Glioblastomas are a devastating form of brain cancer with five year survival rates under 10 percent. From the time of diagnosis, average survival time is less than two years.

"The role of CMV in glioblastoma has been a controversial area of research for several years. These new findings, and especially the dramatic survival rates, suggest that the virus may be an effective target for immune therapy. The results presented by Dr. Mitchell and his colleagues should stimulate more basic research on CMV and its potential therapeutic role in brain tumors and possibly other cancers," said Jane Fountain, Ph.D., program director at the NINDS.

The results showed that administering a tetanus booster before the vaccine increased dendritic cell migration to lymph nodes and also had a significant effect on clinical outcomes. The patients who received the tetanus booster lived more than 36.6 months after diagnosis compared to an average survival time of 18.5 months in those who received dendritic cells alone.

"We did not expect that enhancing dendritic cell migration would be associated with such a dramatic improvement on clinical outcomes in our patients," said Dr. Mitchell.

Next, the investigators used a mouse model to determine how the tetanus booster increased dendritic cell migration to the lymph nodes. The results suggested that giving a booster shot to mice that have received the tetanus vaccine activated a recall response in the exposed T cells. Acting through a chemical messenger known as CCL3, those T cells increased dendritic cell migration to the lymph nodes, which ultimately enhanced the effect of the dendritic cell vaccine on tumor growth suppression.

"Dendritic cell vaccines targeting glioblastoma can be very effective by enhancing migration of dendritic cells. We now understand how we may improve outcomes for patients receiving this type of therapy," said Dr. Mitchell. He added that larger clinical studies need to be conducted to confirm these results.

In addition, more research is necessary to define the role of CMV in glioblastoma and further determine mechanisms to enhance efficacy of vaccines in cancer therapy.

###

This work was supported by grants from the NINDS (NS20023, NS067037) and the National Cancer Institute (CA108786, CA177476, CA134844).

References:

Mitchell et al. "Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients," Nature, March 11, 2015.

The NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Barbara McMakin | EurekAlert!

More articles from Health and Medicine:

nachricht Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering

nachricht New discoveries predict ability to forecast dementia from single molecule
12.12.2018 | UT Southwestern Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

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...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

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...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

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...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

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...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>