An innovative method has been created by researchers to replace a leukemia-affected blood system with healthy donor blood stem cells. The team has shared promising results from animal experiments and laboratory tests with human cells in the journal Nature. The approach involves ‘deleting’ the affected system and building a new, healthy one simultaneously.
In severe cases of leukemia, the only hope for a cure is to replace the unhealthy blood system with a healthy one. Although using donor blood stem cells for transplantation is a well-known treatment, it is a difficult process for patients. First, chemotherapy is used to remove the body’s own blood stem cells as well as most of the blood cells. Only then are the stem cells from a suitable donor given to the patient intravenously by the attending physicians. This procedure comes with side effects and potential complications.
Professor Lukas Jeker’s team from the Department of B has been working on improving this process.
The University of Basel’s iomedicine has taken an innovative approach, as described in the journal Nature, where the team outlines a method for targeted removal of all blood cells in leukemia patients while simultaneously building a new blood system. This successful project was funded by the European Research Council with a Consolidator Grant of EUR 2.4 million.
Blood System Mixer
The researchers in Jeker’s team have developed a system that can be compared to a mixing console, where a DJ gradually decreases the level of the first song while increasing the volume of the vThe volume of the second track gradually increases until the first track completely fades away and only the second track can be heard. The process of fading-down occurs by using specific antibodies attached to a cytotoxic drug which target all blood cells with a particular surface structure. This marker is present in all types of blood cells, including both healthy and diseased ones, but is not found in other cells in the body. As a result, the antibody-drug conjugate progressively identifies and eliminates all cells of the diseased blood system. At the same time, the patient undergoes a transplant of new, healthy blood.
The researchers are finding ways to protect the new blood cells from being attacked by the antibody-drug conjugates. They do this by using genetic engineering to modify the donor stem cells, specifically by making a small change to the surface molecule so that the antibodies don’t recognize the new blood cells. This modification is referred to as “shielding” because it acts as a protective shield against the cancer treatment.
Extensive search for appropriate regulators
the less common types,” said Dr. Matter-Marone. “CD45 fit the bill and was further enhanced with a protective modification to ensure its stability during the fading-down process. This research was a collaborative effort with experts from various fields, and the results are very encouraging for potential future applications in healthcare.””The leukemia cells did not have a certain marker that was found on other cells in the body,” Jeker explains. CD45 met this criteria and could also be modified to “shield” the donor blood stem cells from the cancer treatment while still maintaining its normal function.
Potential uses outside of cancer
“This new method could open up new treatment possibilities for patients who are not able to undergo the chemotherapy required for stem cell transplantation due to their health condition,” says co-author Romina Matter-Marone. AlthThough additional testing and optimization are necessary, the goal is to start initial clinical trials in just a few years. The “mixing console for blood systems” also presents new opportunities, as joint first author Simon Garaudé explains: “We demonstrate how cells that are ‘invisible’ to a blood cell remover can be used to replace the entire blood system.” This is a significant step towards a programmable blood system that could perform functions as needed, such as correcting a severe genetic defect or providing resistance to specific viruses like HIV.
