Genetically modifying donor stem cells with CRISPR technology before a transplant can remove the CD33 protein, successfully protecting healthy blood cells from follow-up immunotherapies and offering a safer path to treat aggressive blood cancers like acute myeloid leukemia, according to a clinical trial published in Nature Medicine.
CRISPR Gene Editing Removes CD33 Protein to Protect Healthy Cells
For aggressive blood cancers, a stem cell transplant may be the only treatment with the potential to cure the disease. Yet, relapses frequently occur, and follow-up options are sparse. Researchers at Washington University School of Medicine in St. Louis and 14 other sites across the U.S. and Canada tested a strategy to make subsequent treatments safer. By utilizing CRISPR gene editing on donor stem cells, the team removed a specific surface protein known as CD33 before performing the transplant.
John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, pointed out that this genetic alteration prevents targeted follow-up treatments from destroying the newly established healthy blood system. Without this modification, therapies aimed at CD33 often mistakenly attack healthy myeloid cells alongside malignant ones, triggering a dangerous inflammatory response and diminishing the potency of the cancer-fighting cells.
Did you know? CD33 is an attractive target for this gene-editing strategy because it appears exclusively on blood-forming cells and is not required for normal stem cell function. People born without the protein show no related health problems, according to trial researchers.
Phase 1/2 Clinical Trial Demonstrates Safe Engraftment in 30 Patients
The multicenter trial enrolled 30 adult patients diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who faced high risks of relapse. Vor Biopharma developed the resulting CD33-deleted stem cell product, known as tremtelectogene empogeditemcel (trem-cel), and funded the research. Following the procedure, all 30 participants achieved successful engraftment by day 28, meaning the modified cells traveled to the bone marrow and began generating new blood cells.
Platelet production rebounded by day 16 on average, matching timelines typically observed in conventional, unedited stem cell transplants. Nineteen participants also received at least one cycle of gemtuzumab ozogamicin—an engineered antibody drug designed to seek out CD33 and deliver a payload directly to cells carrying it. Unlike standard treatments where such maintenance drugs cause dangerous drops in white blood cells, red blood cells, and platelets, these patients maintained stable blood cell counts across the tested doses.
Clinical Insight: While side effects mirrored those of standard transplants—including anemia, low platelets, fever, infections, and graft-versus-host disease—the gene-edited cells successfully shielded patients from the severe blood count drops typically caused by CD33 maintenance drugs.
Single-Case Study Combines Gene Editing with CD33-Targeted CAR-T Cells
Beyond the primary trial, researchers documented a single-case application involving a high-risk AML patient who received the CD33-deleted stem cell transplant. When the aggressive cancer subsequently returned, clinicians treated the patient with CD33-targeted CAR-T cells engineered from T cells supplied by the original stem cell donor.
Published in October 2025 in JCO Precision Oncology, findings from that case showed the patient achieved complete remission and remained cancer-free over a year later. Normal blood cell production recovered entirely, and all circulating blood cells lacked CD33, confirming that the engineered donor cells had firmly established themselves inside the bone marrow.
Frequently Asked Questions
What is tremtelectogene empogeditemcel (trem-cel)?
Trem-cel is a gene-edited donor stem cell product developed by Vor Biopharma that has the CD33 protein removed via CRISPR technology, preventing subsequent CD33-targeted therapies from destroying healthy blood cells.
Why is CD33 targeted in acute myeloid leukemia treatments?
CD33 is present on malignant AML and MDS cells, making it a clear target for immunotherapy, though it also appears on healthy myeloid cells. Removing it from donor stem cells protects the patient’s healthy blood supply during follow-up cancer treatments.
What were the overall survival and safety outcomes in the trial?
Average survival reached just over 14 months among the 30 participants. Seven patients died during the study, with four deaths attributed to cancer progression and three linked to transplant complications such as kidney failure, liver toxicity, and sepsis.
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