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marți, 13 decembrie 2011

Immune Response To Multiple Myeloma Stimulated By Peptide 'Cocktail'

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Immune System / Vaccines
Article Date: 13 Dec 2011 - 4:00 PST

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Scientists at Dana-Farber Cancer Institute have created a "cocktail" of immune-stimulating peptides they believe could provoke the body's defenses to attack multiple myeloma in its early "smoldering" phase and slow or prevent the blood cancer.

Based on laboratory results (abstract 3990) presented at the annual meeting of the American Society of Hematology, the researchers say the immunotherapy approach merits testing in human clinical trials.

The combination of four antigenic peptides derived from myeloma cells sparked a stronger diverse response from immune defenses in laboratory culture than any of the individual peptides, according to the team, led by first author Jooeun Bae, PhD, and senior author Nikhil Munshi, MD.

"Thus, targeting multiple myeloma-associated antigens using a cocktail of specific peptides may provide an effective therapeutic application" in patients with the blood cancer and related diseases, the authors wrote.

Multiple myeloma, in which abnormal blood cells accumulate in bones and other organs, causing life-threatening malfunctions, will be diagnosed in about 20,520 Americans in 2011, according to American Cancer Society estimates, and there will be some 10,610 deaths.

Immunotherapy - getting the body's immune system to recognize cancer cells as "foreign" and then unleash a defensive reaction against them - has proven difficult in multiple myeloma. This type of therapy, also referred to as "cancer vaccines," relies on using a peptide - a piece of a protein from the myeloma cell itself - to spark an immune response.

But multiple myeloma, like many cancers, is a shape-shifting foe: Its tumor-associated antigens can appear and disappear, or undergo mutations that change their identity sufficiently to escape immune detection. For this reason, explained Munshi, previous efforts using a single myeloma antigen have failed to elicit effective immune responses against the disease.

In the new study, the Dana-Farber scientists reasoned that challenging the immune system with not just one, but several myeloma antigens would stand a better chance of prompting a strong reaction. So they identified four antigenic myeloma peptides and tested the ability of each of them to stir a reaction by immune T-cells in a laboratory dish.

Next, the researchers combined all four myeloma peptides into a cocktail: The combination prompted a greater multi-target defensive response against myeloma cells than any of the individual peptides.

Because the myeloma antigens they are studying are derived from human cells, the concept cannot be tested in animals, Munshi says, and therefore the next step will be to administer them in a clinical trial to patients with an early, or "smoldering," form of the blood cancer for which they are not receiving any treatment.

"Some of these patients won't develop the full-blown disease, or won't develop it for several years," Munshi explains. "We would like to find out if giving this peptide cocktail might prevent them from progressing.

"This is an exciting possibility," Munshi adds, "because these patients have good immune systems, and currently there's nothing we can do for them."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our lymphoma / leukemia / myeloma section for the latest news on this subject. Funding for this work was provided by Dana-Farber Cancer Institute.
Co-authors include: Ruben Carrasco, MD, PhD, Weihua Song, MD, Rao Prabhala, PhD and Kenneth C. Anderson, MD, of Dana-Farber and Ann-Hwee Lee, PhD, of Harvard Medical School.
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Communication Via Tiny Protein Triggers Defensive Response In Plants

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Water - Air Quality / Agriculture; Public Health
Article Date: 13 Dec 2011 - 3:00 PST

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Scientists have discovered a new signal that helps invading bacteria communicate but also helps targeted rice plants coordinate defensive attacks on the disease-causing invaders, a finding that could lead to new methods of combatting infection not just in plants, but in humans.

Findings from the study, conducted by a team of researchers led by a University of California, Davis, scientist, were reported in the journal /i>PLoS ONE and in the journal Discovery Medicine.

"Just as invading armies often use coded messages to coordinate attacks on their targets, so single-celled bacteria use biological signals to communicate when they attack plants and animals," said Pamela Ronald, a UC Davis professor of plant pathology and the lead researcher on the study. "Scientists have known this for 20 years, however results from our study reveal a type of bacterial signal that has never been described before."

UC Davis has a long history of tackling agricultural and environmental challenges related to rice production in the United States and around the world. Today, campus researchers are using molecular biology to better understand how to improve the hardiness and yield of this grain, which is a staple food for more than half of the world's population and an important model for plant research.

Up until now, scientists thought that two major groups of bacteria used two distinctly different types of communication codes, Ronald said. However Ax21, the small protein examined in this study, doesn't fit into either of those previously identified communication codes.

Ax21 is made inside the bacterial cell and processed to generate a shorter signal that is secreted outside the bacterium. This signal tips off other bacteria to assemble themselves into elaborate protective bunkers, called biofilms, which make the bacteria resistant to drying out and antibiotic treatment.

"Additionally, Ax21 triggers a change in the expression of nearly 500 bacterial genes, transforming the bacteria from fairly benign organisms into fierce invaders," Ronald said.

"In essence, through communication and communal living, the bacteria increase their chances of survival and proliferation," she said, noting that in rice, the bacteria multiply rapidly in the arteries that transport water, causing the plant to wither and die.

While most rice plants have little defense against the Ax21-mediated bacterial attack, some rice plants carry an immune receptor called XA21 that detects the Ax21 protein produced by the invading bacteria. XA21 belongs to a large class of immune receptors in plants and animals.

The importance of these receptors in immunity is reflected in the awarding of the 2011 Nobel Prize in physiology and medicine to researchers Bruce Beutler of The Scripps Research Institute in La Jolla and Jules Hoffman of the National Center of Scientific Research in Strasbourg, France, for their discoveries of similar receptors in animals.

The new study points out that the Ax21 signaling protein triggers the XA21 immune receptor to biologically alert the plant to launch a powerful defense response against the invading bacteria. The researchers also demonstrated that Ax21 is present in a human disease-causing bacterium that is known to infect hospital patients.

"This study demonstrates that bacteria communicate using private messages. However, plants can intercept these messages and gain a tactical advantage in the evolutionary battle," Ronald said. " It's a fascinating story."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject. Ronald has posted an article about the study on her blog, "Tomorrow's Table," at http://scienceblogs.com/tomorrowstable/.
Researchers collaborating on the study are from UC Davis and Kyung Hee University, Korea.
Funding for the study was provided by the U.S. Department of Agriculture and the National Institutes of Health.
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