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Will Selective CAR T Cells for Acute Myeloid Leukaemia Replace Chemotherapy?

IMMUNOTHERAPY for acute myeloid leukaemia (AML) has shown promise in recent years, and now results from a study that demonstrated improved selectivity with such regimens could help see them become a standard component of AML treatment soon.

Intensive chemotherapy, and sometimes radiotherapy, is the typical treatment given to patients with AML, after which the patients require a haematopoietic stem cell transplant from a healthy donor. The associated side-effect profile makes this treatment approach unsuitable for many patients and puts those who do receive it at risk.

CAR T cells that, when implanted into mice, accurately target both AML initiating cells and healthy haematopoietic stem cells from humans have been developed by scientists from the University of Zurich, University Hospital Zurich, and ETH Zurich in Zurich, Switzerland. By recognising the highly expressed CD117 antigen on AML cells and healthy haematopoietic stem cells, the CAR T-cell therapy can selectively eliminate the cells. Once this has been achieved, the CAR T cells are terminated using a combination of rituximab and the T-cell neutralising antibody treatment antithymocyte globulin. Finally, haematopoiesis is restored in the patient via the receival of a donor stem cell transplant.

Study leader Prof Markus Manz, University Hospital Zurich, said: “Compared to normal strategies, our method works very selectively, meaning that mature blood cells and other tissues are spared.”

These cell culture and mouse-based studies have provided Prof Manz with confidence that the more selective treatment could also be effective in humans, with the potential to one day replace standard chemotherapy conditioning regimens ahead of stem cell transplants. “The principle works: It is possible to eliminate, with high precision, the leukaemic and hematopoietic stem cells in a living organism,” he explained. The research team is eager to initiate human trials but are also exploring the possibility of achieving the same results with simpler constructs, such as T-cell-activating antibodies.