Antibodies directed against cancer stem cells could help patients with acute myeloid leukemia.
An antibody drug that targets a surface marker on cancer stem cells could offer a promising new therapeutic approach for treating acute myeloid leukemia (AML), a form of blood cancer that affects an estimated 50,000 people in Saudi Arabia.
The leukemia stem cells responsible for propagating the disease express a protein on their surface called CD44. Antibodies that block CD44 have been shown to trigger the stem cells to mature, leading to a reduction in the growth and proliferation of these stubbornly hard-to-treat cells. But it wasn’t clear how or why this happens.
Jasmeen Merzaban and her colleagues from King Abdullah University of Science and Technology (KAUST), Saudi Arabia, studied the signaling pathways that change through treatment with a CD44-directed antibody . Working with both human AML cell lines and a mouse model, the researchers showed that inhibiting CD44 with the antibody led to a decrease in the expression of two central pathways implicated in the aberrant growth of cancer cells: the PI3K (phosphoinositide 3-kinase) and the mTOR (mammalian target of rapamycin) pathways.
Notably, the antibody blocked both of the structurally distinct complexes that include mTOR. That’s important because a complete shutdown of mTOR signaling is probably needed to disrupt the multiple feedback loops that can fuel cancer growth, and drugs that only inhibit one of these complexes have in the past, failed to demonstrate a therapeutic benefit for patients with AML.
“A growing body of evidence suggests that a broader inhibitor would result in a more potent therapeutic effect,” said Merzaban.
An anti-CD44 drug like the one tested by Merzaban might just be that broad inhibitor. Encouragingly, in her team’s hands it doesn’t seem to have toxicity issues.
“We show that the anti-CD44 antibody used for our studies had no effect on normal blood cells,” said Samah Gadhoum, a research scientist in Merzaban’s lab group at KAUST and the first author of the study. “However, more work is needed to carefully determine the effect of these antibodies on other cells and other cellular functions within the body.”
Merzaban, Gadhoum and their colleagues are now running follow-up experiments. For now, though, all their results “support the use of anti-CD44 antibodies for the treatment of AML as a differentiation-inducing therapy,” said Merzaban.
As an added bonus: Unlike other therapies that seem to work only for certain forms of the disease, “the interesting thing about CD44-antibody treatment is that it is able to induce differentiation of many more AML subtypes,” said Merzaban.
 Gadhoum, S.Z., Madhoun, N.Y., Abuelela, A.F. & Merzaban, J.S. Anti-CD44 antibodies inhibit both mTORC1 and mTORC2: A new rationale supporting CD44-induced AML differentiation therapy. Leukemia advance online publication 8 August 2016 (doi: 10.1038/leu.2016.221).
Michelle D'Antoni | Research SEA
Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign
Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences