Cancer cells have many strategies for resisting therapy. One is survivin, a protein that drives the division of diseased cells and prevents them from dying. It is found in large quantities in almost all tumours, but is difficult to target with conventional drugs.
Taking this on is a new project led by Shirley Knauer from the Faculty of Biology at the University of Duisburg-Essen in Germany. She and her team are developing bespoke small antibody fragments, nanobodies, which recognise survivin with great selectivity. Because they are smaller and more stable than conventional antibodies, they can reach structures that are virtually inaccessible to other active substances.
The project combines molecular biology, biochemistry and structural biology. The researchers couple the nanobodies to a degradation signal, prompting the cell’s own machinery to break down survivin – a strategy known as targeted protein degradation using PROTACs (proteolysis targeting chimeras). The nanobody binds to survivin, which causes the protein to lose its function and be directed to an enzyme complex that breaks it down. This causes the cancer cell to lose an important protective mechanism.
The researchers hope this will make tumours more responsive to conventional therapies and open up new treatment possibilities. In addition, the modular structure of their method means that it could be transferred to other target proteins in the future.
“Our approach therefore offers great potential for personalised cancer medicine,” Knauer said.
“The funding will enable us to further develop this promising therapeutic platform.”
Jim Cornall is editor of Deeptech Digest and publisher at Ayr Coastal Media. He is an award-winning writer, editor, photographer, broadcaster, designer and author. Contact Jim here.
