New cancer vaccine protein target found

May 25 2008

Cancer Research UK scientists have identified an important new protein target which could be used to produce highly focused vaccine therapies for cancer - according to research published in the Journal of Clinical Investigation*.

Scientists based at Cancer Research UK's London Research Institute have pinpointed a protein unique to dendritic cells. Dendritic cells are responsible for triggering the body's defence system to guard our bodies from pathogens - live organisms that cause disease.

Scientists have been searching for such proteins - or "tags" - for over 30 years but have found very few. It is hoped that new vaccines will be able to home in on the "tag" and direct the body's immune system to specifically attack cancer cells and other pathogens, including HIV or malaria.

Lead author, Dr Caetano Reis e Sousa, said: "Vaccines work by triggering an army of immune cells, called T cells, to attack potentially dangerous foreign molecules, like those found on pathogens. Dendritic cells are the messengers, telling the T cells who to attack.

"We have now found a tag on dendritic cells - called DNGR-1 - which can be targeted by vaccines. Vaccines will carry a sample of the offending molecule and deliver it to DNGR-1 on the dendritic cells. The dendritic cell in turn will present the molecule to the armies of T cells and instruct them to attack."

Since the discovery of dendritic cells in 1973, scientists have been searching for unique tags that could be used to deliver vaccines to those cells, but have only found ones that also exist on other types of cells. Delivering the message to many types of cells is not effective because it could give out contradictory instructions on which molecules to attack, or dilute the message altogether. This is why finding a unique tag on dendritic cells was such an important quest.

Cancer vaccines targeting DNGR-1 will consist of two parts. The first will contain a copy of a unique cancer molecule. This will be the message of "who" to attack. The second part will be a chemical called an adjuvant. This will tell the dendritic cell that the cancer molecule is not safe and that it should command the T cell armies to attack it.

Director of Cancer Research UK's London Research Institute, Dr Richard Treisman, said: "This impressive finding demonstrates how basic research into fundamental mechanisms of immunology can give new insights into how therapeutic cancer vaccines might be developed for the benefit of cancer patients."

Cancer Research UK's director of cancer information, Dr Lesley Walker, said: "Developing treatments that accurately target cancer and have few serious side-effects is one of Cancer Research UK's top goals.

"The results of this research are an important step towards understanding how to create targeted cancer vaccines in the future."

* Tumor therapy via antigen targeting to a novel C-type lectin restricted to dendritic cells. David Sancho et al. 2008. Journal of Clinical Investigation.