Acute myeloid leukemia (AML), the second most common leukemia in children, is hard to treat and has a five-year survival rate of just 65 to 70%, according to the American Cancer Society. While immunotherapies like monoclonal antibodies or CAR T-cell therapy are effective for certain blood cancers, they have not been possible in AML because of toxicity concerns. It's been hard to find targets on leukemia cells that normal blood stem cells don't share, so immunotherapy runs the risk of harming normal cells.
"We decided to engineer the stem cells being transplanted to make them invisible to the immunotherapy," Genovese says.The researchers selected three immunotherapy targets , proteins on the surface ofthat are essential to their survival. They then turned to normal blood stem cells. Using base editing, they swapped in new amino acids in the genes encoding the same proteins.
In a humanized mouse model of AML, the researchers showed that their approach enabled CAR T-cell therapy to eliminate the cancer, with no toxicity to normal blood stem cells—a strong proof-of-concept of its effectiveness and safety., the donor blood stem cells would be pre-treated with base editing. Once the donor cells have engrafted in the bone marrow, patients would receive immunotherapy, which would kill only the leukemia cells.
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