Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Duke Scientists Overcome Immune Resistance In Dendritic Cell Vaccines For Cancer

05.04.2004


Scientists have discovered why dendritic cell vaccines do not attack cancer as forcefully as expected, and they have demonstrated how to overcome this constraint by bolstering the vaccines’ tumor-seeking machinery.



The findings, published in the April 4, 2004, issue of Nature Immunology, present a novel method of equipping dendritic cells so they can activate the immune system to fight against cancers, said the researchers from the Duke Comprehensive Cancer Center and the departments of medicine and immunology at Duke University Medical Center.

Dendritic cells are the "private investigators" of the immune system, detecting foreign proteins in the body -- for example from bacteria and viruses -- and presenting them to "fighter" T-cells for destruction. Scientists turn dendritic cells into cancer vaccines by mixing them with genetic material from the patient’s tumor and infusing the treated cells back into the patient. The dendritic cells present the tumor particles – called antigens – to the fighter T cells, as though pointing out the enemy to a battalion of soldiers.


"Dendritic cell vaccines have shown promise in battling cancers in laboratory studies, but they have not met with quite the success in the clinical trials that laboratory studies suggest they should," said Yiping Yang, M.D., Ph.D., assistant professor of medicine and immunology, the lead author and principal investigator of the study. "Our study highlights what element is missing in dendritic cell vaccines that prevents them from activating the immune system, and we’ve shown how to insert that element."

The major problem, said Yang, is that cancer cells are wily invaders, camouflaging themselves as part and parcel of the body in order to escape detection by the immune system. Dendritic cells present the tumor antigen to T-cells, yet T-cells are curiously tolerant to the antigen and fail to act on its threat.

Yang and his team studied why this tolerance occurs by creating an animal model that mimics the same T-cell tolerance that occurs in cancer patients. They compared the behavior of dendritic cell vaccines in the mice against that of viral vaccines, which have their own limitations but seem to engage T-cell aggression without difficulty.

"We knew there was something unique to viral and bacterial pathogens that mammalian cells don’t have," said Yang.

The scientists found that dendritic cell vaccines failed to remove the "brakes" from fighter T-cells that would allow them to attack the cancer. These brakes are known as regulatory T-cells, and they restrain excessive or unwarranted T-cell aggression.

Yang and his team theorized that removing the regulatory T-cells would remove the brakes from the fighter T-cells. Yet removing all restraints could provoke T-cells to attack the body indiscriminately, potentially causing auto-immune reactions.

In contrast, viral vaccines naturally override these cellular brakes as needed, and Yang’s team determined why that occurs: viruses contain their own unique and foreign molecules that mark them as invaders in the body.

These foreign molecules are known as "pathogen-associated molecule patterns" (PAMPs), and they are unique to viruses, bacteria and other pathogens. They reside on the coating of the bacterium or virus and are separate and apart from the cancer antigen, said Yang. When the viral vaccine presents the tumor antigen to fighter T-cells (via the patient’s dendritic cells), it is also presenting its own PAMPs. The dual signaling – in actuality there are three signals from dendritic cells – provide the needed stimulus to energize T cells into action, said Yang.

"Dendritic cells are viewed by the body as self – even when they are loaded with tumor antigen – because the antigen itself is not enough to provoke fighter T cells to act," said Yang. "If you mix dendritic cells with tumor antigen and PAMPs, then you produce a more potent signal that can break T-cell tolerance."

Further, Yang identified the site on the surface of dendritic cells that recognizes the PAMPs and prompts them to silence regulatory T-cells. The sites are called Toll-like receptors, and activating them is critical to temporarily silencing regulatory T-cells.

"We don’t know the specific chain of events that Toll-like receptors activate inside dendritic cells to temporarily silence regulatory T-cells," said Yang. "But we hypothesize that signals enter through the Toll-like receptors and trigger the release of critical cytokines that tell regulatory T-cells to lie dormant."

Viral vaccines naturally accomplish this task on their own, yet they present their own complex array of limitations, said Yang. First, viral vaccines must be laced with the precise strands of tumor DNA (called tumor-specific antigens) that will spark recognition among the fighter T-cells. However, the tumor-specific antigens for most cancers are unknown, and finding them can be extraordinarily time-consuming and costly. In contrast, dendritic cells can be laced with tumor proteins or RNA that already contain tumor-specific antigens – a much easier task than isolating the antigens, said Yang. Second, viral vaccines must be stripped of their potential to cause illness in the patient.

"We want to merge the strengths of viral vaccines with the ease of using a patient’s own immune system to wage war against the cancer," said Yang.

Thus far, Yang and his team have tested the concept successfully in animals and plan to test the viral vaccines and the bolstered dendritic cell vaccines in lymphoma patients within the next several years.

Becky Levine | dukemed news
Further information:
http://dukemednews.org/news/article.php?id=7502

More articles from Health and Medicine:

nachricht The genes are not to blame
20.07.2018 | Technische Universität München

nachricht Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

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: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>