Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

La Jolla Institute discovers new mechanism for unleashing immune system against cancer

07.04.2014

Finding could lead to new tumor immunotherapy targeting pivotal CTLA-4 protein

A major discovery that brings a new drug target to the increasingly exciting landscape of cancer immunotherapy was published yesterday by researchers from La Jolla Institute for Allergy and Immunology and their collaborators from other institutes.

The study, led by Amnon Altman, Ph.D., and Kok-Fai Kong, Ph.D., is particularly noteworthy because it reveals a new way to block the function of CTLA-4, an immune inhibitory checkpoint receptor already generating huge interest in the pharmaceutical and research communities due to its potential in fighting cancer. An antibody that blocks CTLA-4 is already in use for advanced melanoma.

"These important observations provide new insights into the mechanism of action of CTLA-4 and may provide a novel therapeutic approach against cancer," says Dario Vignali, Ph.D., vice chair and member in the Department of Immunology at St. Jude Children's Research Hospital, who studies immune-based approaches to cancer.

Mitchell Kronenberg, Ph.D., La Jolla Institute president & chief scientific officer, calls the discovery "an extremely important advance" that demonstrates a new way to boost the immune system's ability to recognize and destroy tumors. "This is another example of the growing potential of the immune system as a new and powerful tool in the war on cancer," says Kronenberg.

The finding was published in the prestigious journal Nature Immunology in a paper "Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function." Altman, the La Jolla Institute's director of scientific affairs, and Nicholas Gascoigne, who is a faculty member at Singapore National University and adjunct professor at The Scripps Research Institute in La Jolla, were co-senior authors. Kok-Fai Kong, an instructor in Altman's lab, and Guo Fu, Ph.D., from the Scripps Research Institute were first co-authors. Additional scientists from the La Jolla Institute for Allergy & Immunology, the Scripps Research Institute and the RIKEN Center for Integrative Medical Sciences in Japan collaborated on this study.

In the study, Altman and his team demonstrated a previously unknown – and pivotal -- interaction between an intracellular enzyme Protein Kinase C-η (C-eta) and immune cell receptor CTLA-4 that is critical for the immune suppressive function of regulatory T cells. These cells are a subpopulation of T lymphocytes but, in contrast to most T cells, they suppress or turn down the immune system. This activity is an important component of a healthy immune system, where it serves to dampen exaggerated potentially harmful immune responses that lead to autoimmune diseases and other inflammatory conditions; however, on the flip side, regulatory T cells can also produce the undesirable effect of inhibiting beneficial immune attacks against cancer. CTLA-4 is a protein that sits on the surface of regulatory T cells, where it plays an important role in immune suppression. "The way it works is that this enzyme physically binds to the CTLA-4 receptor," says Altman. "This binding is critical for certain suppressive functions of the regulatory T cells to proceed."

Altman and his colleagues showed that binding of the enzyme to CTLA-4 was essential in order for the regulatory T cells to turn down the immune system in mice. Moreover, by eliminating the enzyme in specially-bred mice the research team also demonstrated that "regulatory T cells lacking this enzyme are unable to suppress the immune system's response against a growing tumor," says Altman.

Another key aspect of the study was the finding that, despite the failure of regulatory T cells lacking Protein Kinase C-η to inhibit an immune response against a growing tumor, these cells retained their ability to inhibit autoimmune disease in a mouse model of inflammatory bowel disease. "This means that you could potentially create a therapy that would allow for a more effective immune response against cancer without the risk of increasing susceptibility to autoimmune diseases," says Altman. "This is quite desirable because it means the mechanism of action is more specific to tumors as opposed to unleashing an overzealous system-wide immune response that can trigger autoimmune diseases."

Altman explains that this result was possibly due to diverse mechanisms utilized by regulatory T cells to suppress different immune responses. "At least some of the mechanisms that regulatory T cells use to inhibit autoimmunity seem not to depend on the association between Protein Kinase C-η and CTLA-4 and, thus, they remain largely operational in regulatory T cells that lack this enzyme," says Altman. "The mechanism we discovered involves a physical contact between regulatory T cells and other critical immune system cells, which may be less important in the autoimmune pathways."

Altman says his next steps will be to test the enzyme's impact in models of additional autoimmune diseases and cancer, and to gain better understanding of how it controls the function of regulatory T cells. The La Jolla Institute is exploring potential industry collaborations to further develop this technology for translation into the clinic.

###

The study was supported in part by funding from the National Institutes of Health, under grant number CA035299.

About La Jolla Institute

Founded in 1988, La Jolla Institute for Allergy and Immunology is a nonprofit, independent biomedical research institute focused on improving human health through increased understanding of the immune system. Its scientists carry out research seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious diseases, cancer, inflammatory, and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes, Crohn's disease and asthma. La Jolla Institute's research staff includes more than 150 Ph.D.s and M.D.s. To learn more about the Institute's work, visit http://www.lji.org.

Bonnie Ward | EurekAlert!

Further reports about: Allergy CTLA-4 Immunology Kinase Protein autoimmune diseases enzyme function immune inflammatory mechanism regulatory

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 >>>