Navigation Links
St. Jude finds molecule that could improve cancer vaccines and therapy for other diseases
Date:11/21/2007

Investigators at St. Jude Children's Research Hospital have discovered a new signaling molecule that prevents immune responses from running amok and damaging the body. The finding could lead to the development of new treatments for cancer, using vaccines; for autoimmune diseases, such as Type 1 diabetes; and for inflammatory diseases, such as inflammatory bowel disease (IBD) and asthma.

The St. Jude team discovered that specialized immune lymphocytes called regulatory T cells release a protein complex composed of two proteins called Ebi3 and Il12a. This protein complex acts like a brake on the activity of the aggressive immune cells called effector T lymphocytes. A report on this discovery appears in the journal Nature Nov. 22, 2007.

The newly recognized protein complex is one of a large group of signaling molecules called cytokines that cells use to communicate with each other. Since the immune system cytokines are called interleukins, the St. Jude team named this protein interleukin-35 (IL-35). Most cytokines stimulate immune system cells by driving the immune attack or causing inflammation. However, IL-35 is one of the few signaling molecules known to inhibit immune system activity.

The discovery of IL-35 is important because the manipulation of regulatory T cells is a key goal of immunotherapy, said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology, and the papers senior author. Immunotherapy is the treatment of infections, cancer or other diseases by manipulating the immune system to enhance or restrict its activity. Despite the fact that regulatory T cell-mediated immunotherapy holds promise for patients, the molecules responsible for the cells ability to suppress immune system activity are largely unknown, a problem that has slowed progress in this field.

The St. Jude team showed that the genes that produce IL-35 (Ebi3 and II12a) are active in regulatory T cells but not in effector T cells and are critical to regulatory T cell function. In fact, regulatory T cells that lack the Ebi3 and II12a genes lose much of their ability to suppress effector T cells. In addition, these regulatory T cells are unable to cure mouse models of an inflammatory disease that closely resembles human IBD.

When the researchers added regulatory T cells to a culture dish with effector T cells, the regulatory T cells dramatically increased their production of the decoded forms (messenger RNA) of the Ebi3 and II12a genes. This suggests that effector T cells had released signals that stimulated the regulatory T cells to decode these genes and make IL-35, the researchers reported.

The identification of IL-35 as a key cytokine released by regulatory T cells adds significantly to our understanding of how these cells prevent immune responses from running out of control and causing damage, Vignali said. Regulatory T cells are seen as a major impediment to the development of effective anti-cancer vaccines and may prevent sterilizing immunity in certain chronic infections, such as hepatitis C and tuberculosis. As the maximal suppressive function of regulatory T cell is dependent on IL-35, blocking its activity may reduce regulatory T cell function and reduce their ability to block anti-tumor immune responses. Thus, treatments that block IL-35 activity may make anti-cancer vaccines more effective. Vaccines work by stimulating the immune system to recognize and attack specific targets, such as germs or cancer cells.

Autoimmune diseases and inflammatory diseases are caused by a breakdown of the normal regulatory processes that control our immune system, Vignali said. Novel treatments that add IL-35 or boost IL-35 activity may also provide new therapeutic opportunities for these diseases.

The identification of IL-35 is especially exciting because, to date, it is the only known cytokine that is made specifically by regulatory T lymphocytes and can suppress the activity of effector T cells directly, said Lauren Collison, Ph.D., a postdoctoral fellow in Vignalis laboratory who contributed significantly to the project. This suggests that controlling levels of IL-35 in patients might one day allow clinicians to dial the immune response up or down depending on the needs of the patient. Collison is the papers first author.


'/>"/>

Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
Source:Eurekalert

Related medicine news :

1. Penn study finds pro-death proteins required to regulate healthy immune function
2. MRI finds breast cancer before it becomes dangerous
3. RAND finds cases of undiagnosed diabetes drop sharply
4. Children of depressed moms do better when dad is involved, SLU researcher finds
5. Ability to cope with stress can increase good cholesterol in older white men, study finds
6. Pitt study finds inequality in tobacco advertising
7. Study finds some kids are being misdiagnosed with asthma
8. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
9. Parents perceptions can hamper kids asthma care, study finds
10. Study finds primary care depression treatment often does not follow quality guidelines
11. Study of Studies Finds No Risk to Children From Phthalates in Toys
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/27/2017)... ... March 27, 2017 , ... M&S ... Certificate of Conformity for the Smart System® 20/20. CE Certification builds upon M&S's ... standards and specifications such as ANSI, ISO and proven test methods used in ...
(Date:3/27/2017)... PA (PRWEB) , ... March 27, 2017 , ... ... business simulation -centric training, today announced the launch of a new research ... strategy, having the skills needed to execute that strategy, and the actual success ...
(Date:3/27/2017)... ... March 27, 2017 , ... According to the American Cancer ... stages, is more than 95%. Once the cancer spreads to other organs, bones, or ... find out how to avoid this latter group, tune in to Lifestyle Magazine ...
(Date:3/27/2017)... Texas (PRWEB) , ... March 27, 2017 , ... ... at the GTEC Orange facility from 8:00am-10:00am on Monday, April 3rd to commemorate ... and will be an opportunity for area-residents to celebrate two great years while ...
(Date:3/25/2017)... PA (PRWEB) , ... March 25, 2017 , ... Getting ... as a public relations partner. , All through the year, Garden Media aims ... press releases, working with key influencers and pitching client’s key messages to ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... India , March 24, 2017 Abdominal Aortic Aneurysm Repair ... million by 2022, Globally, registering a CAGR of 5.1% from 2016 to 2022. The ... projected to dominate the market during the study period. ... ... ...
(Date:3/24/2017)... , March 24, 2017 New England Pediatric ... of an award including funding and in-kind service towards ... technology.  "Making blood draws less traumatic ... their whole hospital experience better.  We,re looking forward to ... can help improve care for the kids we treat," ...
(Date:3/24/2017)... 2017 Research and Markets has announced the addition ... Demand Forecast to 2022" report to their offering. ... The global wound care market was worth ... CAGR of 6.7% during 2016-2022 Among the various wound care ... in the global market in 2015. Among the various applications, surgical wound ...
Breaking Medicine Technology: