Washington University study uses CRISPR gene editing to treat blood cancer
- A clinical trial published in Nature Medicine reveals that genetically modifying donor stem cells before transplantation can shield healthy cells from follow-up cancer treatments.
- CAR-T cell therapy has achieved high success rates against certain aggressive blood cancers, but it struggles against acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
- Researchers removed a specific protein called CD33 from the donor cells to make the resulting healthy blood cells invulnerable to therapies designed to target that protein.
A clinical trial published in Nature Medicine reveals that genetically modifying donor stem cells before transplantation can shield healthy cells from follow-up cancer treatments. Across 14 medical centers throughout the U.S. and Canada in addition to Siteman Cancer Center—located at WashU Medicine and Barnes-Jewish Hospital—Louis spearheaded the research to tackle a major barrier in managing aggressive blood cancers like myelodysplastic syndrome and acute myeloid leukemia.
Overcoming CAR-T Therapy Limitations in Blood Cancers
CAR-T cell therapy has achieved high success rates against certain aggressive blood cancers, but it struggles against acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). John F. DiPersio, corresponding author and director of WashU Medicine’s Center for Gene and Cellular Immunotherapy, explained that many proteins found on AML and MDS cells also appear on healthy myeloid cells and donor stem cells.
When CAR-T cells are programmed to attack these shared proteins, they frequently destroy healthy blood stem cells alongside the cancer. This collateral damage can trigger a severe inflammatory response while simultaneously diluting the treatment’s effectiveness, as large numbers of CAR-T cells concentrate on healthy targets instead of malignant ones. The foundational concept to bypass this barrier was initially described by Miriam Y. Kim, now an assistant professor of medicine at WashU Medicine.
Removing CD33 via CRISPR Gene Editing
Researchers removed a specific protein called CD33 from the donor cells to make the resulting healthy blood cells invulnerable to therapies designed to target that protein.
We are encouraged by the results of this study showing that a CD33-deleted stem cell transplant looks very similar to the outcomes of standard stem cell transplantation.
John F. DiPersio, Washington University School of Medicine
DiPersio noted that the team hopes to combine this approach with CD33-targeted immunotherapies, such as CAR-T cells, to expand treatment options for patients facing these aggressive malignancies. CD33 serves as an effective target because it appears exclusively on blood-forming cells rather than other tissues. Evidence indicates that CD33 is not strictly required for normal blood stem cell function, as individuals born without the protein display no related health problems.
Clinical Outcomes and Remission Case Study
In a separate study published in October 2025 in JCO Precision Oncology, DiPersio and his collaborators detailed a single case of high-risk AML involving a patient who received a CD33-deleted stem cell transplant. When the patient’s cancer subsequently returned, physicians administered CD33-targeted CAR-T cells derived from T cells provided by the original stem cell donor.
The patient entered complete remission and stayed cancer-free for more than a year following the CAR-T treatment. Normal blood cell production also recovered, and all circulating blood cells lacked CD33, confirming that the genetically modified donor cells had successfully engrafted and established themselves in the bone marrow.
