Vaccine Immunotherapy Targets Breast Cancer

OB/GYN News,  March 15, 2000  by Bruce Jancin

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SAN ANTONIO -- Vaccine immunotherapy has emerged as a promising approach in the treatment of breast cancer, Dr. Martin A. Cheever reported at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

Early clinical trials are already underway for several prototypical candidate vaccines and are contemplated for various others.

Vaccines that are designed to boost specific immunity against breast cancer will probably work best in early-stage disease, in which the postsurgical tumor burden is relatively low, the cancer cells have not yet evolved sophisticated escape mechanisms, and the patient has not been saddled with severe immunoincompetence due to extensive chemotherapy said Dr. Cheever of Corixa, a Seattle biotechnology company.

Enthusiasm for a vaccine approach to breast cancer therapy has waxed and waned over the years. It is at a high level now because of credible evidence that breast cancers express antigens that are recognized by the immune system and that vaccination can boost specific immunity against these antigens.

There is great appeal in the notion that a vaccine approach will provide specificity in its attack and will lack cross-reactive toxicity with chemotherapy Dr. Cheever noted.

Much of the vaccine development effort to date has focused on HER2/neu as a target antigen. This antigen is commonly overexpressed in breast cancer and is associated with aggressive disease. In a phase I clinical trial conducted at the University of Washington in Seattle, HER2/neu vaccines elicited a favorable specific T-cell response.

"We now know that an immune response [to a HER2/neu vaccine] can be generated. What we're spending substantial effort on right now is trying to formulate it in order to induce immune responses to all areas of the immune system, meaning helper T-cell responses, cytotoxic T-cell responses, and antibody responses, and also eliciting consistent and high-level responses in the majority of patients. After that will come issues of efficacy as well as toxicity," he explained.

But why should researchers bother trying to develop a HER2/neu vaccine when trastuzumab (Herceptin), Genentech's monoclonal antibody directed against HER2/neu, is already on the market? Because a vaccine is potentially more effective. Monoclonal antibodies recognize and bind only to antigens on the cell surface. In contrast, the T-cell responses that are elicited by a vaccine can also recognize intracellular antigens. That should translate into greater cancer cell killing, Dr. Cheever said.

The major potential downside of a HER2/neu vaccine at this point is that the antigen also is produced by normal cells, albeit at low levels. This raises the possibility that such a vaccine could induce autoimmune destruction of normal tissue, he added.

Other target antigens now in ongoing or proposed vaccine trials include B899, MUC-1, and STn antigens.

Another promising vaccine target is mammaglobin. This protein appears to be a marker for breast epithelial proliferation. It is expressed in more than 80% of primary breast cancers and is present in the serum of some affected patients.

Fueling the drive to develop vaccine immunotherapy against breast cancer is the tremendous power that is now available for the discovery of target antigens, observed Dr. Cheever.

"Very soon, as an offshoot of the Human Genome Project, all proteins expressed by breast cancer will be known, and all proteins expressed by normal cells in the body will be known. At that point, virtually every potential breast cancer antigen will be known or will be knowable," he noted.

COPYRIGHT 2000 International Medical News Group
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