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, email@example.com (323) 361-8505
Ellin Kavanagh | Eurek Alert!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences