Researchers have developed a new approach aimed at “deleting” a blood system affected by leukemia and replacing it with a healthy system using donor blood stem cells. The team, led by Professor Lukas Jeker from the University of Basel, published their findings in the journal Nature, detailing successful results from animal experiments and human cell studies. In aggressive cases of leukemia, this method offers a potential cure by replacing the diseased blood system with a healthy one, potentially revolutionizing current treatment methods.
Traditionally, leukemia treatment involves chemotherapy to eliminate the body’s own blood stem cells, followed by a transplant of donor stem cells. This process is associated with side effects and complications, making it burdensome for patients. The team’s innovative approach involves using specific antibodies coupled with a cytotoxic drug to target and destroy all blood cells in the patient’s body, including both healthy and diseased cells. Simultaneously, new healthy blood cells from a donor are transplanted, allowing for the gradual transition to a new, healthy blood system while minimizing potential complications.
The researchers compared this process to a mixing console, where the levels of different “songs” are adjusted to fade out the original blood system while introducing the new one. By modifying the donor stem cells to shield them from the effects of the cytotoxic drug, the team ensured that the new blood cells would not be targeted during the fading-out process. This targeted modification, referred to as “shielding,” effectively protected the donor stem cells and allowed for the successful establishment of a healthy blood system in the patient.
The study’s first authors, Simon Garaudé and Dr. Romina Matter-Marone, collaborated with an interdisciplinary team to identify the most suitable target structure and protective modification for the fading-out process. CD45, a surface molecule present on all blood cells, was chosen for its ability to meet the necessary criteria for both targeting and shielding. The molecule was found to be effective in trials on mice and human cells in the laboratory, demonstrating its potential for use in future clinical applications.
Beyond leukemia treatment, the new approach opens up possibilities for addressing other health conditions that are incompatible with chemotherapy, offering new treatment options for patients in need of stem cell transplantation. The researchers envision the potential for further applications, such as creating a programmable blood system that could correct genetic defects or provide resistance to specific viruses like HIV. With further testing and optimization, initial clinical trials using this innovative method could begin in the near future, marking a significant advancement in the field of blood system regeneration.