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 Exploring a new frontier of cyber-physical systems: The human body
18.05.2015 | National Science Foundation

nachricht Soft-tissue engineering for hard-working cartilage
18.05.2015 | Technische Universitaet Muenchen

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: Basel Physicists Develop Efficient Method of Signal Transmission from Nanocomponents

Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.

Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...

Im Focus: IoT-based Advanced Automobile Parking Navigation System

Development and implementation of an advanced automobile parking navigation platform for parking services

To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...

Im Focus: First electrical car ferry in the world in operation in Norway now

  • Siemens delivers electric propulsion system and charging stations with lithium-ion batteries charged from hydro power
  • Ferry only uses 150 kilowatt hours (kWh) per route and reduces cost of fuel by 60 percent
  • Milestone on the road to operating emission-free ferries

The world's first electrical car and passenger ferry powered by batteries has entered service in Norway. The ferry only uses 150 kWh per route, which...

Im Focus: Into the ice – RV Polarstern opens the arctic season by setting course for Spitsbergen

On Tuesday, 19 May 2015 the research icebreaker Polarstern will leave its home port in Bremerhaven, setting a course for the Arctic. Led by Dr Ilka Peeken from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) a team of 53 researchers from 11 countries will investigate the effects of climate change in the Arctic, from the surface ice floes down to the seafloor.

RV Polarstern will enter the sea-ice zone north of Spitsbergen. Covering two shallow regions on their way to deeper waters, the scientists on board will focus...

Im Focus: Gel filled with nanosponges cleans up MRSA infections

Nanoengineers at the University of California, San Diego developed a gel filled with toxin-absorbing nanosponges that could lead to an effective treatment for skin and wound infections caused by MRSA (methicillin-resistant Staphylococcus aureus), an antibiotic-resistant bacteria. This "nanosponge-hydrogel" minimized the growth of skin lesions on mice infected with MRSA - without the use of antibiotics. The researchers recently published their findings online in Advanced Materials.

To make the nanosponge-hydrogel, the team mixed nanosponges, which are nanoparticles that absorb dangerous toxins produced by MRSA, E. coli and other...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International symposium: trends in spatial analysis and modelling for a more sustainable land use

20.05.2015 | Event News

15th conference of the International Association of Colloid and Interface Scientists

18.05.2015 | Event News

EHFG 2015: Securing health in Europe. Balancing priorities, sharing responsibilities

12.05.2015 | Event News

 
Latest News

Mesoporous Particles for the Development of Drug Delivery System Safe to Human Bodies

22.05.2015 | Materials Sciences

Computing at the Speed of Light

22.05.2015 | Information Technology

Development of Gold Nanoparticles That Control Osteogenic Differentiation of Stem Cells

22.05.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>