Gene-edited stem cells may enable safer CAR-T therapy for blood cancers
In a 30-patient trial, researchers used CRISPR to remove the CD33 protein from donor stem cells before transplantation. This allowed a CD33-targeted cancer treatment to attack leukemia cells while sparing the edited healthy cells. The approach could expand CAR-T therapy to acute myeloid leukemia and myelodysplastic syndrome.
The 30-patient trial, conducted at Siteman Cancer Center and 14 other sites across the U.S. and Canada, used CRISPR to delete the CD33 surface protein from donor stem cells before transplantation. Results published in Nature Medicine showed the edited cells engrafted successfully and appeared to shield healthy blood cells from CD33-targeted treatments, with outcomes resembling standard transplantation.
The strategy addresses a key limitation of CAR-T therapy for AML and MDS: these cancers share surface proteins with healthy myeloid cells, causing CAR-T cells to attack both. Miriam Y. Kim, who first described the concept during postdoctoral work at the University of Pennsylvania and later at WashU Medicine, helped bring the idea to clinical testing. Researchers hope to eventually pair edited transplants with CD33-directed immunotherapies.
This approach could meaningfully expand treatment options for patients with AML and MDS, who currently face limited choices when cancer returns after transplantation. By making healthy cells invisible to targeted therapies, the strategy may allow more aggressive post-transplant treatment without destroying the patient's new blood system. If confirmed in larger studies, it could also influence how other cancers with shared surface proteins are approached, potentially broadening the reach of CAR-T therapy beyond its current applications.