Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune therapy could treat leukemias, autoimmune diseases, transplant rejection

13.10.2005


In studies with mice, treatment with a new monoclonal antibody that targets immune system B cells has shown considerable promise for treating leukemias, autoimmune diseases and transplant rejection, according to immunologists at Duke University Medical Center.



B cells are the immune system’s "arms factories," producing antibodies that target invading microbes for destruction. Abnormal B cell proliferation causes such leukemias as multiple myeloma and acute lymphoblastic leukemia, and such autoimmune diseases as rheumatoid arthritis and lupus.

The researchers, led by Professor and Chair of Immunology Thomas Tedder, Ph.D., reported their findings in the online Early Edition of the Proceedings of the National Academy of Sciences the week of Oct. 10, 2005. Other co-authors of the paper were Norhito Yazawa, Yasuhito Hamaguchi and Jonathan Poe in Tedder’s laboratory. The research was sponsored by the National Institutes of Health.


Monoclonal antibodies (mAbs) are those created to target a specific protein. In their studies, the Duke researchers used mAbs targeting a protein called CD19 that is found on the surface of B cells. As their experimental animal models, they used mice that had been genetically altered to produce a human version of the CD19 protein on their B cells.

Their studies demonstrated that CD19 mAbs did tag B cells containing that protein, and that these B cells were then destroyed by the immune system.

When the researchers administered the CD19 mAbs to the mice, they found that it greatly depleted mature B cells, as well as precursor and immature B cells in the animals. The depletion of precursor and immature B cells is important because aberrant versions of such cells cause a number of leukemias and other malignancies where new therapies are needed, said Tedder.

And, they found that giving the mice CD19 mAbs, along with a mAb that targets another B cell protein, CD20, resulted in additive effects on B cell depletion. A CD20 mAb is now marketed as Rituximab.

Importantly, the researchers found that the CD19 mAb treatment dramatically depleted growth of malignant B cell tumors in the animals. In ten mice transplanted with malignant B cell lymphomas, the CD19 mAb treatment prevented the appearance of circulating and tissue tumor cells for up to seven weeks in all the animals. In contrast, all untreated mice died from their tumors by three weeks.

"We were actually quite shocked at how effectively CD19 mAb-treatments prevented malignant B cell expansion," said Tedder. "Treatment of such tumors in mouse models is extraordinarily difficult."

Finally, when the researchers measured the effects of CD19 mAb treatment on blood levels of antibodies produced by B cells, they found a significant reduction in circulating antibody levels as well as B cell mediated "humoral immune responses" in the animals, including reductions in autoantibodies of the type produced in autoimmune diseases and transplant rejection.

According to Tedder, the results of the CD19 mAb animal studies warrant rapid advance to clinical trials for treatment of B cell leukemias and other malignancies that derive from early B cell precursors and perhaps antibody-producing B cells.

The CD19 mAbs may show broader effectiveness than Rituximab, he said, because CD20 is expressed only by mature B cells, in contrast to CD19, which is expressed by both mature and immature B cells and by antibody-producing cells.

Tedder noted that in general such immunotherapies are likely to produce far fewer side effects than current chemotherapies -- which can produce secondary malignancies, sterility and growth retardation in children who take them for leukemias.

In particular, the researchers’ finding that the treatment greatly depletes B cells in the peritoneum -- a major source of autoantibody-producing cells in mice -- could make it an effective treatment for autoimmune diseases such as lupus, said Tedder.

"In addition, this treatment could greatly aid transplant patients who require multiple organ transplants because they develop a humoral antibody response to their transplanted organs, or they already have preformed antibodies that prevent them from accepting some donor grafts." In contrast to the potentially benign nature of the CD19 mAb treatment for such patients, current therapy involves removing the spleen and giving such patients chemotherapeutic treatment and plasmapheresis to remove antibodies from the blood.

Tedder and his Duke colleagues are now developing plans for clinical trials at Duke of the CD19 mAbs in leukemias as well as autoimmune diseases. Also, a company that he founded, Cellective Therapeutics, Inc., will be further developing the therapy.

Dennis Meredith | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Research team of the HAW Hamburg reanimated ancestral microbe from the depth of the earth
01.03.2017 | Hochschule für Angewandte Wissenschaften Hamburg

nachricht Researchers Imitate Molecular Crowding in Cells
01.03.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

A better way to measure the stiffness of cancer cells

01.03.2017 | Health and Medicine

Exploring the mysteries of supercooled water

01.03.2017 | Physics and Astronomy

Research team of the HAW Hamburg reanimated ancestral microbe from the depth of the earth

01.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>