Targeting aggressive childhood leukemia with nanobody PROTACs

Scientists at the University of Duisburg-Essen are researching new therapies for aggressive forms of childhood leukemia. For the first time, their approach tries to distinguish between two subtypes using so-called nanobody PROTACs. These attack diseased tissue while sparing healthy cells. The José Carreras Leukaemia Foundation is supporting the project, led by Prof. Dr. Shirley Knauer and Dr. Mike Blueggel from the Faculty of Biology, with 143,740 euros for two years.

The research focuses on molecules that break down certain proteins in cancer cells: nanobody PROTACs (proteolysis targeting chimeras). They couple a binding molecule for the target protein with a signal that causes the cell to destroy this particular protein. This allows a disease-relevant protein to be removed in a targeted manner without damaging healthy structures.

The target protein in this case is the enzyme Taspase 1, which plays a central role in particularly aggressive forms of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). So far, it has been difficult to develop effective strategies against this enzyme. Therefore, researchers are now exploiting differences in the internal degradation machinery of cancer cells for the first time: they want to develop PROTACs that specifically degrade Taspase 1 in the respective form of leukemia.

Another innovation is the use of so-called helicons - small spiral-shaped proteins that, as part of biological PROTACs, establish a connection with the degradation factors described above. This enables the targeted destruction of the protein of interest.

With this dual novel approach, we are opening up an entirely new avenue for personalised leukemia treatment. This project could be groundbreaking, not only for research, but also for the long-term treatment of these particularly aggressive diseases.'

Dr. Mike Blueggel