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Nanobody technology offers promise for stopping cancer spread

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Research Highlights
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New research carried out at the University of Leeds, in collaboration with the CRUK Scotland Institute and the University of Cambridge, has led to the discovery of a nanobody that offers a potential new approach for preventing the spread of cancer, known as metastasis.

A protein called Fascin-1, which is found at high levels in metastatic cancer (stage IV cancer), is instrumental in allowing cancer cells to grow finger-like surface protrusions known as filopodia that they use to move around.

The new nanobody, Nb 3E11, interacts with Fascin-1 and prevents it from carrying out its role in the formation of filopodia.

Nb 3E11 was discovered by Dr Selena Burgess at the University of Leeds, where facilities such as X-ray crystallography and mass spectrometry were used to study its interaction with Fascin-1. It’s effect on filopodia in cancer cells was then studied by scientists at the CRUK Scotland Institute.

Scientists made a nanobody library specific to Fascin-1 using using blood from two llamas that had been immunised with Fascin-1 protein. Nanobodies against Fascin-1 were then identified using biochemical screening methods to search the library.

The Fascin-1-binding nanobodies found were classified into 14 families based on their amino acid sequence and a representative nanobody from each group was tested. 13 of the nanobodies did not affect the activity of Fascin-1. But one did - Nb 3E11.

When Nb 3E11 was introduced into cancer cell models, it was shown to significantly reduce the formation of filopodia on the surface of the cells.

Nanobodies are small antibody fragments derived from heavy-chain only antibodies -a class of antibody that is only produced by the immune systems of certain animals including llamas, camels and sharks.

Nanobodies have caught the attention of scientists as they can bind to targets with similar affinity and specificity as full-sized antibodies but are easier and cheaper to produce. There are nanobodies in clinical trials for the treatment of cancer, rheumatoid arthritis and psoriasis.

Read the full press release on the Faculty of Biological Sciences website.

Read A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation on Open Biology.