Antibody Extends Life of Mice with Breast Cancer

BUFFALO, N.Y. -- A monoclonal antibody developed by researchers at the University at Buffalo has been shown to extend significantly the survival of mice with human breast-cancer tumors and to inhibit the cancer's spread to the lungs in the animals by more than 50 percent.

The antibody, named JAA-F11, targets a particular disaccharide, an antigen known as TF-Ag, which aids the adhesion and spread of certain cancer cells. While the antibody did not kill the cancer cells, it blocked stages of cancer-cell growth that allow the cells to adhere to organ tissue, the research showed.

Results of the research appeared in the November 2006 issue of the journal Neoplasia.

Mice with breast-cancer tumors that received the antibody had a median survival time of 72 days, compared to 57 days for the animals that did not receive JAA-F11, the study found. In addition, exposing cultures of tumor cells to the antibody inhibited cell growth by a statistically significant 16 percent.

Kate Rittenhouse-Olson, Ph.D., associate professor of clinical and laboratory sciences in the UB School of Medicine and Biomedical Sciences, is senior author on the study.

"This antibody binds with a carbohydrate on the tumor cell surface that is involved in adhesion of the cell during the metastatic process," said Rittenhouse-Olson. "Not only would drugs attached to the antibody JAA-F11 bind to the tumor cell surface to direct their cytotoxic effect, but the binding of the antibody itself would block the cell from metastasizing."

The antibody was tested using in vitro models of tumor cell growth, in assays to determine its ability to damage or kill cells (cytotoxicity), in various models of cancer metastasis, and, finally, in mice with metastatic breast cancer.

"In addition to providing a survival advantage," said Rittenhouse-Olson, "JAA-F11 immunotherapy reduced the metastatic tumor burden significantly, reflected by both a dramatic decline in the overall incidence of spontaneous metastasis to the lung -- 88 percent to 47 percent -- and fewer macroscopic metastatic lesions."

The research group currently is determining if JAA-F11 could increase the effectiveness of existing cancer drugs, she said, as well as studying the possibility of using the antibody as a vehicle for the targeted delivery of drugs to aid cancer diagnosis and therapy.

Jamie Heimburg and Jun Yan, co-first authors on the paper, were graduate students in Rittenhouse-Olson's lab at the time of the study.

Also contributing to the research were Susan Morey and Robert Klick, Ph.D., from the UB Department of Biotechnical and Clinical Laboratory Sciences; Linda Wild, M.D., from UB's Pathology Department; Olga V. Glinskii, M.D., Vladislav V. Glinsky, M.D., and Virginia H. Huxley, Ph.D., from the University of Missouri, and Rene Roy, Ph.D., from the University of Quebec in Montreal. Glinsky also is affiliated with the Harry S. Truman Memorial Veterans Hospital in Columbia, Mo.

The research was supported by grants from the National Institutes of Health to Rittenhouse-Olson, Glinskii and Huxley; from the VA Merit Review Program to Glinsky, and from the U.S. Department of Defense to Heimberg and Rittenhouse-Olson.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The School of Medicine and Biomedical Sciences is one of five schools that constitute UB's Academic Health Center.