UW group's work on breast cancer vaccine moves forward

UW researchers in collaboration with the Seattle-based biotechnology company, Corixa Corp., have determined that the HER-2/neu protein, which is produced, or "expressed," by some breast and ovarian cancer cells, can stimulate an immune response in cancer patients. A recent human study confirms that this response can be boosted by vaccination in patients with breast and ovarian cancer.

The development of cancer vaccines is among several new approaches to cancer therapy that target specific cancer-causing proteins.

"This is the first step toward the long-term goal of developing a vaccine that we think may prevent recurrence of cancer in patients whose tumors express an excessive amount of the HER-2/neu protein," says Dr. Mary L. Disis. Disis is a UW associate professor of medicine and an affiliate investigator in the Fred Hutchinson Cancer Research Center's Clinical Research Division.

Disis and her group of Seattle-based researchers, together with investigators at Corixa, are taking a leading role in making prevention of recurrent breast cancer a reality. Last week, Disis presented the group's progress to the U.S. Department of Defense Breast Cancer Research Program "Era of Hope" meeting in Atlanta.

Disis and her colleagues base their work on the discovery that many tumors elicit a naturally occurring immune response in cancer patients. This means that the body is treating some tumor components as foreign tissue. The response, however, is typically at a very low level and inadequate to thwart recurrence of the cancerous cells.

The identification of the HER-2 "self-protein" as a tumor antigen was the first step in turning up the "volume" on the body's response to cancer cells. This self-protein is associated with human breast and ovarian cancers and other adenocarcinomas, including some lung and prostate tumors.

Disis and her colleagues at Corixa have identified some of the immune-response activating portions of the HER-2 self-protein and have manipulated these protein fragments, or peptides, to optimize their capacity to trigger an immune system vs. tumor response.

The first round of human trials of the HER-2/neu vaccine is complete and the results are promising. The study included 64 patients, all of whom prior to the study had completed treatment for Stage III or IV breast, ovarian or lung cancer and had undergone treatment to the point of maximal response. Some patients had no evidence of disease prior to the study; others had existing disease but were stable on hormonal therapy. In this study Leukine^® (GM-CSF) was used as a vaccine adjuvant.

The majority of patients developed some measurable HER-2/neu peptide- and protein-specific immune responses. A quarter of the patients were followed for the persistence of immune response after a series of immunizations was completed. Approximately 50 percent of the patients remaining in follow-up have persistent detectable immunity up to two years after the completion of the study.

"Our group, as well as groups working with other tumor antigen systems, has shown that measurable tumor-specific immune responses can be generated by vaccinating cancer patients. The next critical question is whether that immune response has any effect on tumor growth," says Disis.

Safety is a foremost concern. To date, the researchers have detected no occurrence of inadvertent immunity-versus-body, or autoimmune, reactions to "innocent" tissues producing the HER-2 protein. Long-term follow-up and further trials testing other formulations of the vaccine are under way.

The research team includes biomedical scientists from the University of Washington, Corixa Corp., and Immunex Corp., manufacturer of Leukine.

The U.S. Army Medical Research and Material Command supports this, and other breast cancer research, through congressional funding for the eradication of breast cancer. ¶

Jeanette Ruby