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Visualising cancer interactions

20 July 2009

A molecular image revealing the interaction between skin cancer cells and T-cells – the cells which protect our body against disease - has been produced by the School of Medicine.

How the immune system sees skin cancerHow the immune system sees skin cancer

A team led by Professor Andy Sewell of the School’s Infection, Immunity and Inflammation interdisciplinary research group used X-ray crystallography to determine the molecular conformation of a human cancer antigen – a protein that can generate immune responses - in complex with a human T-cell receptor. Their findings are published in the Journal of Biological Chemistry.

The ability to see how such molecules look is of paramount importance to modern medicine and drug design. They are far too small to see in detail even with the most advanced light microscopes, so the Cardiff team used X-rays to look at the molecules in solid crystalline form.

The research revealed the first images of how killer T-cells use a molecule on their surface called a T-cell receptor to identify another molecule that is present at much higher levels on the surface of human melanoma cells compared to healthy tissue. This molecular recognition results in the destruction of these cancerous cells. This structure is now being used to design better cancer vaccines.

Killer T-cells can use their T-cell receptor to recognise and kill human cancer cellsKiller T-cells can use their T-cell receptor to recognise and kill human cancer cells

Professor Sewell said: "We anticipate wide interest in this structure as it is only the second human cancer/T-cell receptor complex ever solved. Our T-cells are really designed to eliminate ‘foreign’ molecules and they are crucial for the elimination of pathogens. T-cells perform less well at eliminating cancer as cancer cells are derived from our own tissue and pose the immune system with a greater challenge."

Dr David Cole, School of Medicine and the report’s first author said: "This structure has important implications for cancer vaccine design. Now we can visualize these interactions we can begin to improve them. We have already improved the affinity of this particular interaction by over 20 million fold as part of our unpublished research. This structure has been essential for allowing us to see what is happening at the atomic level. I am thrilled to get this result first as we knew that we were in a race with several other groups around the world. "

The School has recently made considerable investment in X-Ray crystallography, with the appointment of Dr Pierre Rizkallah, a scientist who used to run the central protein X-ray beams at the world-leading Daresbury Laboratory in Warrington. More widely, the University has also invested in this area, with the appointment of Nobel Laureate Professor Robert Huber and the recruitment of Dr Matthias Bochtler to the School of Chemistry.

Commenting on the research, Dean of the School of Medicine Professor Paul Morgan said: "The solving of this structure was facilitated by the investment that the School made in appointing an expert in protein crystallography, Dr Pierre Rizkallah. We expect that this team will solve many more important structures in the near future."

The research was partially funded by the Cardiff University Link Chair scheme and is published in the Journal of Biological Chemistry.

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