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The researchers used the novel cell therapy called CAR-T. This therapy uses genetic modification to equip human immune cells with a receptor, thanks to which they can systematically dock onto only the leukemic stem cells and the healthy hematopoietic stem cells and destroy them. This creates space for the new donor cells to be transplanted. To avoid that the genetically modified immune cells then also attack the hematopoietic stem cells from the donor, the CAR-T cells are deactivated after they have done their work and before the transplant. This is done by using an antibody against a surface marker of the CAR-T cells. After the donor stem cell transplant, they take their place in the bone marrow and begin to rebuild the hematopoietic and immune system. Clinical use of selective immune-mediated elimination planned
The results were achieved using cell cultures in the lab and in mice with human blood and cancer cells. But Markus Manz is confident that the treatment could also be effective in humans: "The principle works: It is possible to eliminate, with high precision, the leukemic and hematopoietic stem cells in a living organism." Researchers are currently testing whether the method is only possible with CAR-T cells or also with simpler constructs - such as T-cell-activating antibodies. As soon as the pre-clinical work is completed, Manz wants to test the new immunotherapy in a clinical study with humans. "If our method also works with humans, it could replace chemotherapy with its serious side effects, which would be a great benefit for patients with acute myeloid leukemia or other hematopoietic stem cell diseases," explains Manz. Source:
University of Zurich Journal reference:
Myburgh, R., et al . (2020) Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells. Leukemia . doi.org/10.1038/s41375-020-0818-9 .
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