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University of Glasgow researchers have successfully used the first bioengineered bone marrow model to carry out vital cancer research, offering new insights into potential therapies for the disease.
The breakthrough is documented in a new study, published in the journal Biomaterials, and represents an important step forward in being able to carry out medical research without the use of animals.
The study details the efficacy of CAR T-cell therapy – a promising new blood cancer treatment – in targeting acute myeloid leukaemia (AML), the most common leukaemia in adults. Researchers say their new bioengineered model has been able to deliver the kind of human-relevant insights and information that current research methods that rely on animal models have so far been unable to achieve.
Now, a team led by scientists at the University of Glasgow has been able to successfully carry out research on leukaemic HSCs by inserting them into bioengineered jelly-like substances, called hydrogels, that mimic the natural bone marrow environment. The team then targeted the cancer cells with CAR T-cell therapy to find out if it could effectively target the disease. While this is an early-stage study, the approach opens the door to more accurate pre-clinical testing, which - over the next decade - could help improve the development of safer and more effective therapies.
While CAR T-cell therapy has shown promise for other blood cancers, its application to AML has been hindered by a number of issues, including toxicity to local healthy cells. Using their bioengineered stem cell model the team were able to provide key new information on the efficacy and safety of CAR T-cell therapy for AML. They found that, conventional testing methods - typically cells in a Petri dish - both overestimated the effectiveness of CAR T-cell therapy and failed to predict its harmful effects on healthy cells – issues that were detected using the bioengineered tissue model. The new findings have clear implications not only for future research on CAR T-cell therapy for AML, but also on approaches to pre-clinical CAR T-cell testing.
Dr Hannah Donnelly, one of the lead authors of the study and research fellow at the University of Glasgow said: “There is a major translational gap in cell therapy development – conventional, over-simplified testing methods often fail to predict how therapies will behave in humans. This gap leads to high failure rates in clinical trials, driving up costs and delaying treatments for patients.
The study, ‘Synthetic peptide hydrogels as a model of the bone marrow niche demonstrate efficacy of a combined CRISPR-CAR T-cell therapy for acute myeloid leukaemia’ is published in Biomaterials. This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC).
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