The main complication following allogeneic hematopoietic stem cell transplantation is acute graft-versus-host-disease (aGvHD). Besides conventional immunosuppresive agents, OKT3-antibodies, interleukin-2 receptor antibodies or anti-thymocyte globulin to name just a few are also being used to treat this disease, though they are often associated with low-level long-term success and toxic side effects. In addition, these types of therapy suppress the entire immune system and with this also the immunologically significant anti-tumor effect of the immune cells (graft-versus-leukemia effect). This GvL effect must however be maintained in order to prevent the risk of the underlying disease (leukemia) returning in the patient.
Due to the need for innovative and less stressful forms of therapy, murine GvHD and leukemia transplantation models were developed within the unit. These models were able to be used, among other things, to establish human immune systems in mice. In due consideration of the GvL effect, these models enable the testing of active agents for the prevention and treatment of GvHD, which would be immediately conceivable for clinical application on human subjects. The focus is on the investigation of the influence of various anti-human CD4 antibodies on the GvHD with due regard to the GvL effect. So far, it could be demonstrated, for example, that the emergence of aGvHD following allogeneic hematopoietic stem cell transplantation could be prevented in the long term through the ex vivo incubation of a transplant with the anti-human CD4 antibody MAX.16H5. This involved the use of a mouse model which also displays features of the human immune system.
A GvHD-NOD/SCID mouse model and a leukemia mouse model will be further developed at a later stage in the project. Furthermore, anti-CD4 antibodies will be introduced in the treatment and prevention of GvHD as therapeutic agents until clinical application is possible. New findings from antibody therapy for the transplantation of solid organs and for other immunological disease patterns (e.g. autoimmune diseases) will also be deduced. Besides a new type of antibody therapy, insights into immunological processes of GvHD and the GvL effect are to be expected. These insights may be extremely valuable not just for hematopoietic stem cell transplantation, but also for the transplantation of solid organs and for application in other indications (e.g. autoimmune diseases).