A piece of research has shown that it is possible to eliminate stem cells related to human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer, using a new targeted therapy.
Associate Professor Richard Lock, from the Children's Cancer Institute Australia and the University of New South Wales, has revealed that the new therapeutic approach has been found to selectively attack human cancer cells grown in the lab as well as in animal models of leukemia.
AdvertisementAML is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy.
"The cellular and molecular basis for this dismal picture is unclear. However, previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance," says Lock.
LSCs are cells that can initiate AML and are critical for its long-term growth.
Lock and his colleagues exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells.
The researchers created a therapeutic antibody that recognized and bound to CD123, hoping that the antibody would selectively interfere with AML-LSC survival.
When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signalling in the tumour cells was blocked.
The research team also observed that 7G3 impaired migration of the AML-LSCs to bone marrow, and activated the innate immune system of the host mouse to destroy the AML-LSCs.
They say that, overall, treatment with 7G3 substantially improved mouse survival when compared with control groups.
Lock and his colleagues are currently using a CD123-targeting antibody in phase 1 clinical trials of advanced AML. They say that there are no signs of treatment-related toxicity.
These results hold substantial promise for future cancer therapeutics.
"The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials," concludes Associate Professor Lock.
A research article on the study has been published in the journal Cell Stem Cell.
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