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
Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases
Injecting gene cocktail into mouse pancreas leads to humanlike tumors
06.04.2018 | University of Texas Health Science Center at San Antonio
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
The Atlantic overturning – one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards – is weaker today than any time before in more than 1000 years. Sea surface temperature data analysis provides new evidence that this major ocean circulation has slowed down by roughly 15 percent since the middle of the 20th century, according to a study published in the highly renowned journal Nature by an international team of scientists. Human-made climate change is a prime suspect for these worrying observations.
“We detected a specific pattern of ocean cooling south of Greenland and unusual warming off the US coast – which is highly characteristic for a slowdown of the...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Power and Electrical Engineering
19.04.2018 | Life Sciences
18.04.2018 | Materials Sciences