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 'Icebreaker' protein opens genome for t cell development, Penn researchers find
21.02.2018 | University of Pennsylvania School of Medicine

nachricht Similarities found in cancer initiation in kidney, liver, stomach, pancreas
21.02.2018 | Washington University School of Medicine

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Researchers invent tiny, light-powered wires to modulate brain's electrical signals

21.02.2018 | Life Sciences

The “Holy Grail” of peptide chemistry: Making peptide active agents available orally

21.02.2018 | Life Sciences

Atomic structure of ultrasound material not what anyone expected

21.02.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>