Wir überwinden Grenzen

For some leukemias, transplantation of foreign blood stem cells is the only possible therapy. However, in more than every second patient, the new immune cells attack the patient's body. This dangerous rejection reaction can be activated or intensified if intestinal bacteria pass through the damaged intestinal wall into the blood. Together with Swiss colleagues, researchers at the Freiburg University Medical Center have now successfully tested a vaccination in mice that combats the invading bacteria and thus largely prevents the rejection reaction. Only one in ten animals developed the dangerous graft-versus-host immune reaction. The study by the Freiburg researchers was published on September 16, 2019 in the journal Proceedings of the National Academy of Sciences.

"The vaccinations are a completely new approach that could help us to get a major risk of stem cell transplants under control," says Prof. Dr. Robert Zeiser, Head of the Department of Tumor Immunology at the Department of Internal Medicine I at the Freiburg University Medical Center.

Active and passive vaccination work

The researchers administered a medicinal antibody to the animals that binds to the bacteria that had entered the blood. Marked in this way, the bacteria were quickly recognized by the immune system and destroyed in a targeted manner. A dangerous rejection reaction was largely absent, and the diversity of bacteria in the intestine, which is important for recovery, was not attacked. "The use of antibodies could be superior to the antibiotics used to date. In particular, the bacteria that migrate into the intestinal wall are killed without damaging the intestinal flora," says Zeiser. This type of antibody administration is also known as passive vaccination.

Active vaccination was also successful. For this, the animals were injected with low doses of the bacterial surface proteins. "In this way, the immune system learns to fight the bacteria in a targeted manner and the excessive reaction does not occur," says Zeiser. In a previous study, the researchers had shown that the bacteria invading through the intestine trigger the life-threatening graft-versus-host defense reaction. However, it will probably be several years before such vaccinations can be used in patients.

Original title of the publication: Immunization against Poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity

DOI: 10.1073/pnas.1908549116

Link to the study: www.pnas.org/content/early/2019/09/12/1908549116

Contact: 
Prof. Dr. Robert Zeiser 
Head of the Division of Tumor Immunology 
Department of Internal Medicine I (focus: Hematology, Oncology, Stem Cell Transplantation) 
Freiburg University Medical Center 
Phone: 0761 270-34580 
robert.zeiser@uniklinik-freiburg.de