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Three New Targets Found for Cancer Vaccines Study adds to the list of genes that might help the body fight cancer

New York (March 13)--Investigators at the Ludwig Institute for Cancer Research have discovered three new genes that may prompt the immune system to seek out and destroy cancer cells. The genes belong to a specialized group of proteins known as Cancer/Testis (CT) antigens.

Antigens are what the body relies on to identify intruders. In certain tumors, CT antigens are abnormally expressed, acting as a target for killer T-cells to attack. Although CT antigens do not generally elicit enough immune cells to destroy tumors on their own, the findings may lead to new treatments that help the immune system finish the job.

"CT antigens are probably the most highly restricted tumor antigens we know of," said Dr. Mathew Scanlan, Assistant Member of the Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering, and lead author of the study. "By having a clear target to hit--and more of them--we can design highly select treatment vaccines that bolster the body's natural ability to fight cancer."

The results appear in the April issue of the International Journal of Cancer. As a fast track article, the study was posted on the Journal's Web site prior to the April publication date.

CT antigens are normally expressed in developing reproductive cells, but in adults they are found only in male testis and in tumors. Previous research has identified 14 CT antigens. Dr. Scanlan's team found three new CT antigens by reviewing entries in the Unigene database, a computer program that archives nearly 3.5 million DNA sequences. They also reviewed RNA expression patterns in a more specialized database, called SAGE.

After narrowing the search down to 73 candidate genes, the Ludwig researchers analyzed both normal and cancerous tissue samples. They discovered a new CT antigen, named CT 15, which was expressed in renal cancer. The other two, CT 16 and CT 17, were found in a wide range of cancers.

Scientists have made considerable progress in finding new targets that could prove useful for antigen-specific cancer vaccines. There are four main types of tumor antigens: CT, differentiation, overexpressed, and viral.

CT antigens are of particular interest because in addition to promoting an immune response, they do not cause killer T-cells to attack healthy tissue. With the exception of some germ cells, CT antigens are found only in tumors, making it likely that any immune response from these antigens will be highly selective in going after cancer.

"Modified vaccines can target CT antigens in tumors with very little risk of harming healthy cells," said Dr. Scanlan. "Such specific treatments may cause fewer side-effects."

Finding additional targets, he said, will be of critical importance in designing vaccines that strike several antigens at once.

"Tumors can evolve, so they may lose certain antigens over time," Dr. Scanlon said. "If you want to make up for the loss of one target, you need to have others to back you up."

The Ludwig Institute for Cancer Research is a non-profit global research organization with branches in seven different countries. More than 900 scientists and support staff from around the world conduct basic and clinical research at the Institute, focusing on cancer genetics and genomics, tumor immunology, and cell growth and differentiation.

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