For aggressive blood cancers like acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), a stem cell transplant can be curative—but relapse leaves few options. A new clinical trial tested whether CRISPR-editing donor stem cells to remove the CD33 protein could make follow-up treatments safer. The edited cells, called trem-cel, were transplanted into 30 patients at high risk of relapse. The cells took hold in the bone marrow and produced blood cells that lacked CD33, according to results published in Nature Medicine.
The idea addresses a key limitation of CAR-T therapy. CAR-T cells work well against some blood cancers, but in AML and MDS many of the target proteins also appear on healthy myeloid cells, including donor stem cells. Attacking those shared proteins can destroy the healthy transplanted cells and trigger a dangerous inflammatory response. By removing CD33 from donor stem cells, the researchers aimed to create a blood system that could withstand CD33-targeted therapy.
To test that protection, patients received the CD33-targeting drug gemtuzumab ozogamicin after transplantation. The edited cells appeared to shield healthy blood cells from the drug, and the transplant outcomes looked similar to standard stem cell transplantation. In a separate reported case, a patient with high-risk AML who relapsed after a CD33-deleted transplant received CD33-targeted CAR-T cells from the same donor and entered complete remission, remaining cancer-free more than a year later.
The study was led by researchers at Washington University School of Medicine and conducted at 15 sites in the U.S. and Canada. It was funded by Vor Biopharma, which developed trem-cel. The authors say the approach could eventually be combined with CD33-targeted immunotherapies to improve treatment for patients with these aggressive cancers.