Allogeneic haematopoietic cell transplantation has been an established curative treatment option for diseases of the blood-forming system, such as leukaemia, for decades. In this procedure, the patient's diseased or degenerated blood cells are first eliminated and replaced with healthy cells from a donor. The transplanted stem and immune cells settle in the recipient and from then on produce new, functional blood cells – including T and B cells, which are crucial for the immune defence.

Despite careful donor selection, in which tissue characteristics are matched as closely as possible, serious immune reactions can often occur after haematopoietic cell transplantation (HCT). The transplanted T cells may recognise the recipient's own cells as foreign, which can lead to graft-versus-host disease (GVHD). Studies show that up to 50% of all HCTs are accompanied by relevant GVHD progression.

Previous strategies for preventing severe GvHD have often been based on systemic immunosuppression. However, these non-specific treatments can themselves cause side effects, such as promoting opportunistic infections or increasing the risk of cancer recurrence.

The Fraunhofer IZI research team has further developed a targeted prevention strategy that enables the transplanted T cells to become immunotolerant to the recipient's tissue without impairing the overall function of the immune system.

To achieve this, the donor's immune cells are treated outside the body prior to infusion using special antibodies that target the surface molecule CD4 on the T cells. The targeted blockade of the CD4 molecule functionally restricts the activation of GvHD-inducing immune cells and significantly reduces the risk of developing acute GvHD.

Comprehensive molecular and cellular analyses have now enabled the central mechanism of action to be characterised. Experimental in vivo models have shown that a single treatment of donor T cells with the anti-CD4 antibody prior to transplantation can reduce GvHD over the entire observation period. "The results suggest that this approach can effectively reduce the risk of acute GvHD and thus has the potential to improve treatment outcomes for patients. However, the final evaluation must be carried out in clinical trials," said Prof. Stephan Fricke, head of the study. Based on these promising preclinical data, the novel strategy is now being prepared for clinical translation in a Phase I/II trial.

Funding information:

Significant parts of the studies were co-financed with funds from the EU (ERDF/ESF) and tax revenues based on the budget approved by the Saxon State Parliament (funding code 100382841).

Significant parts of the study were co-financed within the framework of the Cluster4Future "SaxoCell" with funds from the Federal Ministry of Education and Research (now BMFTR).