Researchers at Children's Hospital Los Angeles have discovered that by targeting a particular receptor, chemotherapy-resistant cancer cells can be killed in an acute form of childhood leukemia, offering the potential for a future treatment for patients who would otherwise experience relapse of their disease.
Nora Heisterkamp, PhD, and colleagues at The Saban Research Institute of Children's Hospital Los Angeles have discovered that by targeting the B-cell activating receptor (BAFF-R), chemotherapy-resistant precursor B acute lymphoblastic leukemia cells (pre-B ALL) can be selectively killed in vivo and in vitro. Results will be published on May 13 in Molecular Cancer Therapeutics.
This is Nora Heisterkamp, Ph.D.
Credit: Children's Hospital Los Angeles
Acute lymphoblastic leukemia (ALL) is characterized by an excessive amount of white blood cell precursors, called B-cell lymphoblasts, in the blood and bone marrow. B-cell lineage ALL (pre-B ALL) accounts for 80 to 85% of childhood ALL. Although the cure rate has increased, further advances can only be achieved by identifying mechanisms to treat specific subsets of chemotherapy-resistant leukemia cells.
In a previous study (Leukemia, 2013), the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts, making selective killing of ALL cells possible by targeting this receptor.
"We've now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells," said Heisterkamp, who is also professor of Research, Pediatrics and Pathology at the Keck School of Medicine of the University of Southern California.
Using a genetically-engineered antibody (anti-BAFF-R monoclonal antibody), Heisterkamp and colleagues have demonstrated that the BAFF-R could be successfully blocked in a dose-dependent manner. Inhibition of BAFF-R function rendered leukemia cells less viable in mouse models of the disease. Also, the presence of this antibody on the pre-B ALL cells resulted in increased killing of the cancer cells by natural killer (NK) cells and macrophages.
"We found that human pre-B ALL cells could be even further reduced when the anti-BAFF-R antibody was combined with chemotherapy or another therapeutic agent," said Heisterkamp. "We are looking at a potential one, two punch." Heisterkamp and her colleagues will continue to evaluate the use of this antibody for the treatment of ALL.
Co-authors include Reshmi Parameswaran, Min Lim, Fei Fei, Hisham Abdel-Azim, Anna Arutyunyan, Isabelle Schiffer, John Groffen, of The Saban Research Institute of Children's Hospital Los Angeles; and Margaret E. McLaughlin, Hermann Gram, Heather Huet, of Novartis Institute for Biomedical Research.
Funding for this research came from National Institutes of Health grants PHS CA090321, CA 172040, Alex's Lemonade Stand Foundation for Childhood Cancer, the V-Foundation for Cancer Research and Novartis Pharmaceuticals.
About Children's Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children's hospital in California and among the top five in the nation for clinical excellence with its selection to the prestigious US News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States, is one of America's premier teaching hospitals and has been affiliated with the Keck School of Medicine of the University of Southern California since 1932.
Media Contact: Ellin Kavanagh, firstname.lastname@example.org (323) 361-8505
Ellin Kavanagh | Eurek Alert!
Columbia Engineering team develops targeted drug delivery to lung
03.09.2015 | Columbia University School of Engineering and Applied Science
Reward, aversion behaviors activated through same brain pathways
03.09.2015 | Washington University School of Medicine
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE have developed a highly compact and efficient inverter for use in uninterruptible power...
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
03.09.2015 | Event News
20.08.2015 | Event News
20.08.2015 | Event News
03.09.2015 | Process Engineering
03.09.2015 | Materials Sciences
03.09.2015 | Materials Sciences