Some of the most dangerous blood cancers are extremely difficult to cure. Diseases such as acute myeloid leukemia, often called AML, and myelodysplastic syndrome, known as MDS, can grow quickly and become resistant to treatment.
For many patients with these aggressive cancers, a stem cell transplant may be the only chance for long-term survival.
A stem cell transplant works by replacing damaged or cancer-filled blood-forming cells with healthy donor stem cells.
These donor cells move into the bone marrow and begin producing healthy blood cells again. Although this treatment can save lives, it also carries serious risks. Even after a successful transplant, the cancer can still return.
Doctors have also been trying to combine stem cell transplants with newer immune therapies such as CAR-T cell therapy. CAR-T therapy uses specially engineered immune cells that are trained to find and destroy cancer cells.
This treatment has already transformed care for some blood cancers, but it has not worked well for all forms of leukemia.
One major problem is that many blood cancers share the same surface proteins as healthy blood-forming cells. This means CAR-T cells can accidentally attack healthy cells along with cancer cells, causing dangerous side effects and reducing the effectiveness of treatment.
Now, researchers at Washington University School of Medicine in St. Louis have developed a new approach that may solve part of this problem.
Their clinical trial used donor stem cells that were genetically edited before transplantation. The scientists removed a protein called CD33 from the donor cells using CRISPR gene-editing technology.
The results, published in Nature Medicine, suggest the approach may help protect healthy donor cells while allowing future cancer-targeting therapies to work more effectively.
The study was led by Dr. John F. DiPersio at Washington University School of Medicine and involved researchers from Siteman Cancer Center and multiple hospitals across the United States and Canada.
CD33 is a protein commonly found on AML and MDS cancer cells. Unfortunately, healthy blood-forming cells also carry CD33. Because of this, therapies designed to attack CD33 often damage healthy cells too.
Researchers believed that removing CD33 from donor stem cells might solve this problem. If the healthy donor cells no longer carry CD33, future therapies aimed at CD33 could focus more directly on the cancer.
Scientists chose CD33 carefully because previous research suggested the protein is not essential for normal blood cell function. Some people are naturally born without CD33 and appear healthy.
In the trial, 30 adults with high-risk AML or MDS received stem cell transplants using donor cells that had CD33 removed through CRISPR gene editing. The engineered stem cell product is known as tremtelectogene empogeditemcel, or trem-cel.
After the transplant, patients also received a maintenance therapy called gemtuzumab ozogamicin. This therapy targets CD33 and carries an anti-cancer drug directly to cancer cells. The treatment is already approved for some AML patients but can cause serious side effects because it also damages healthy blood cells.
The researchers wanted to see whether the CD33-deleted stem cells could protect patients from these toxic effects.
The results were encouraging. All patients successfully achieved engraftment within 28 days, meaning the donor stem cells settled into the bone marrow and began producing new blood cells. Some patients recovered even sooner.
Importantly, blood cell production remained stable during the maintenance therapy, suggesting the edited stem cells were protected from damage. This may allow doctors to use stronger anti-cancer therapies without causing dangerously low blood counts.
The average survival time in the study was slightly more than 14 months. Nineteen patients received at least one cycle of the maintenance therapy, and researchers were able to determine a recommended treatment dose.
The study also included side effects commonly seen after standard stem cell transplants. Some patients developed infections, anemia, low platelet counts, fever, or graft-versus-host disease, a condition in which donor immune cells attack healthy tissues.
Seven patients died during the study. Four deaths were caused by cancer progression, while three were linked to transplant complications including kidney failure, liver toxicity, and sepsis.
The researchers also described an especially promising case involving a patient with one of the most aggressive forms of AML. After receiving the CD33-deleted stem cell transplant, the patient later experienced a relapse and was treated with CD33-targeted CAR-T cell therapy using immune cells from the same donor.
The patient achieved complete remission and remained cancer-free more than one year later. The patient’s blood cells also lacked CD33, showing that the edited donor stem cells had successfully established themselves in the bone marrow.
Researchers believe this could represent an important step toward safer and more targeted blood cancer treatment. By protecting healthy donor cells through gene editing, doctors may eventually combine stem cell transplants with powerful CAR-T therapies more safely.
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Source: Washington University School of Medicine in St. Louis.
