SUMMARY OF RESEARCH BEING UNDERTAKEN

The most life-threatening aspect of Recessive Dystrophic Epidermolysis Bullosa (RDEB) is that patients develop skin cancer. Usually these types of skin cancer, called squamous carcinoma (SCC), are not life-threatening as they do not spread to other parts of the body. Sadly, the SCCs that develop in people with RDEB do spread to other areas. Thus to help RDEB patients we must either find a means to stop the cancers developing or stop the ones that do develop from spreading. This project is designed as a strategy to target the second option; stop the cancers spreading.

Several years ago Dr Marshall’s laboratory discovered that SCC cancer cells invade the local tissues by means of a protein that appears on the surface of all the cancer cells. This protein, called alphav-beta6, does not appear on normal skin. They found in the laboratory that if you stopped the alphav-beta6 on cancer cells, from binding to the proteins in the local environment, this stopped their ability to invade.

In this study two types of alphav-beta6 blocking-drugs will be made. Firstly, they have already made some progress designing new drugs based on their knowledge of the proteins to which alphav-beta6 usually binds. These new drugs are based on small fragments of these proteins and are called peptides.

The second type of drug is based on antibodies. Antibodies are large proteins in the blood that bind to, and therefore block the ability to function, of foreign bodies such as viruses and bacteria. The part of the antibody that recognises the “antigen” on the foreign body is only a tiny fragment at the tip of the antibody. Scientists have found methods to produce only this tip of the antibody and still retain the ability to recognise antigens. These mini-antibodies are called single-chain Fv (scFv). There are so-called “libraries” of scFv that contain hundreds of millions of different scFv, each one recognising a different antigen. Using laboratory tricks those scFv that can recognise and inhibit the function of alphav-beta6 will be identified. The scFv will then be turned back into whole antibodies for injection into RDEB patients in the hope that this will help stop the skin cancers spreading.