Universal approach could potentially expand CAR T cell therapy to all blood cancers
A broad new strategy could hold hope for treating virtually all blood cancers with CAR T cell therapy, which is currently approved for five subtypes of blood cancer. Scientists in the Perelman School of Medicine at the University of Pennsylvania have demonstrated the potential efficacy of this approach in preclinical tests.
In the study, published today in Science Translational Medicine, the researchers used engineered CAR T cells to target CD45-;a surface marker found on nearly all blood cells, including nearly all blood cancer cells. Because CD45 is found on healthy blood cells too, the research team used CRISPR base-editing to develop a method called "epitope editing" to overcome the challenges of an anti-CD45 strategy, which would otherwise result in low blood counts, with potentially life-threating side effects.
Because the strategy results in replacing the stem cells that create new blood cells, it also has potential use as a milder form of chemotherapy conditioning, which is given to patients before a bone marrow transplant to suppress the immune system.
The researchers tested the strategy in an extensive set of experiments in cell culture and mice models. They showed that the new approach not only keeps anti-CD45 CAR T cells from attacking each other or stem cells, but also enables swift destruction of blood cell cancers.
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