Peptide provides target for a cancer killer.

Ovarian and breast cancer cells, like other malignant cells, may have an Achilles' heel after all. Researchers now report that part of the immune system will kill malignant cells that display a telltale protein fragment (peptide) on their surface. This finding may lead to the development of a therapy that magnifies the body's own attack on such cancers.

Previously, researchers had identified several warning peptides on the surface of cancerous pigment-producing skin cells. Yet malignant melanoma, the deadliest form of skin cancer, accounts for just 1 percent of all cancer deaths. George E. Peoples and Timothy J. Eberlein of Brigham and Women's Hospital in Boston and their colleagues wondered if they could nab a peptide that would target the much more common breast and ovarian cancers.

In the Jan. 17 Proceedings of the Nation al Academy of Sciences, the researchers report synthesizing a nine-amino-acid peptide they call GP2. This peptide, when held in place by another molecule on the cell surface, presents an inviting target for the immune system. In this case, a type of T lymphocyte (a white cell) destroys cells carrying the GP2 target, the researchers say.

The instructions for building this peptide come from a gene called HER2/neu. Some researchers believe this gene codes for a protein that enables breast, ovarian, and other body cells to divide. In the fetus, HER2/neu cranks out its protein product, making fast-paced growth possible. In most adult cells, however, this gene remains relatively inactive. Scientists believe these cancers result when the gene goes into high gear in an adult cell.

In their experiment, Eberlein's team ground up fresh tumor samples taken from women with ovarian or breast cancer. Next, they isolated the cytotoxic T lymphocytes, killer white cells that destroy tumors. The researchers found that such T cells taken from breast tumors destroy malignant ovarian cells displaying the GP2 peptide. Likewise, they showed that such cells taken from ovarian tumors decimate cancerous breast cells bearing the same target. The team suspects that T cells trained to recognize GP2 in the test tube will become more efficient at killing tumors in the body.

Indeed, the researchers believe that killer T cells will home in on any malignant cell displaying the GP2 peptide. Although healthy cells occasionally display GP2, the immune system goes on red alert only when it notices cells showing lots of this peptide. If the researchers can translate these findings into therapy, it may benefit not only people with breast and ovarian cancer, but those with gastric cancer and one type of lung cancer as well, Eberlein says.

The researchers are beginning to fashion a treatment based on the immune system's reaction to GP2. They plan to remove killer T cells from tumors of patients and culture those cells with GP2 in order to spur recognition of this target. Then the researchers would inject the primed T cells back into the patient. Alternatively, doctors could give cancer patients GP2 directly, in an effort to rev up the T cells in the body.

To create an effective therapy, researchers would have to give patients a cocktail of different peptide targets, says Olivera Finn, an immunologist at the University of Pittsburgh School of Medicine. Those peptides would spur killer T cells to recognize not just one, but several targets on the malignant cancer cell, she adds. Researchers believe some cancer cells evade detection by producing an altered peptide. "If that tumor can be targeted three or more ways...it's not likely to escape," Finn says.

In the future, such research may lead to an actual vaccine for cancer. Eberlein and others believe that a mix of peptides given to an individual at high risk of cancer may provide the edge the immune system needs to rout a malignant growth before it gets a foothold in the body.