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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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How Patients Will Respond To Immunomodulator Therapy For Multiple Myeloma

Main Category: Lymphoma / Leukemia / Myeloma
Article Date: 13 Dec 2011 - 0:00 PST

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Research on the same protein that was a primary mediator of the birth defects caused by thalidomide now holds hope in the battle against multiple myeloma, says the study's senior investigator, Keith Stewart, M.B., Ch.B. of Mayo Clinic in Arizona. Dr. Stewart presented the results at the 53rd annual meeting of the American Society of Hematology in San Diego.

The drug thalidomide achieved infamy in the early 1960s as the cause of severe birth defects after being given to pregnant mothers for morning sickness. However, this drug, along with the highly related compounds lenalidomide and pomalidomide, also help to treat blood cancers, and are used worldwide as a cornerstone of therapy for the bone marrow cancer multiple myeloma. These drugs modulate the immune system and together are called immunomodulators or IMiDs.

The exact mechanisms and targets through which these therapies work to enhance immune response or kill cancer cells have been largely unknown. As a result, knowing which patients to treat and how to separate out the positive properties of these drugs from side effects has been impossible.

After recent research identified a protein known as cereblon as a primary mediator of the birth defects caused by thalidomide, researchers theorized that cereblon may also orchestrate the anti-tumor properties and be the primary therapeutic target for multiple myeloma.

In this study, researchers tested the theory and found a possible link between resistance to IMiDs and presence of cereblon. The researchers then found that lowering the level of cereblon allows the IMiDs to work properly.

"Interestingly, some resistant patients had normal cereblon levels, suggesting that while cereblon may be an absolute requirement for response, there are likely other mechanisms present that play a role in drug resistance," says Dr. Stewart. "These findings help us understand which patients may be more or less likely to respond to therapy and allow us to focus on other ways we can target cereblon as a possible biomarker to improve treatment and patient outcomes in multiple myeloma. This work also suggests that we can begin to dissect out the cause of birth defects from the anti-cancer properties and develop safer drugs in the future."

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. Other researchers involved in the study include Yuan Xiao Zhu, Esteban Braggio, Ph.D., Chang-Xin Shi, Jessica Schmidt, Laura Bruins, Steven Schuster, M.D., Rafael Fonseca, M.D. and, Leif Bergsagel,M.D., of Mayo Clinic and Chad Bjorklund, Ph.D. and Robert Orlowski, Ph.D., M.D., of MD Anderson Cancer Center.
Mayo Clinic Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Mayo Clinic. "How Patients Will Respond To Immunomodulator Therapy For Multiple Myeloma." Medical News Today. MediLexicon, Intl., 13 Dec. 2011. Web.
13 Dec. 2011. APA

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All opinions are moderated before being included (to stop spam)

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Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.



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