Seeking that ounce of prevention

Imagine if you could treat or prevent breast cancer, or ovarian cancer, with a simple shot in the arm.

That is the goal of researchers at the University of Washington and the Fred Hutchinson Cancer Center.

Dr. Mary "Nora" Disis, a UW and Fred Hutch scientist, is leading the effort to find an effective cancer vaccine, using an approach known as immunotherapy that, in the context of cancer care, was once dismissed by many experts as bordering on quackery.

An experimental vaccine based on Disis' earlier findings is being tested in breast cancer patients who have been treated but remain at high risk of relapse, to see if the vaccine can prevent the cancer from recurring.

She is now trying the same approach with ovarian cancer.

If the goal of a cancer vaccine sounds futuristic, it may help to consider just how timeworn is the current state of the art in cancer care. Radiation therapy started in 1896, one year after X-rays were discovered, and chemotherapy grew from medical observations made while treating World War I victims of chemical weapons, specifically the blistering agent known as mustard gas.

Disis thinks one of the most promising new approaches to cancer care will be to immunize us against the disease. "Most patients do mount an immune response to cancer," Disis said. "The question is if those immune responses mean anything."

Until fairly recently, the medical establishment generally answered that question with a resounding no. Those like Disis working on immunotherapy for cancer often were dismissed as misguided -- if not downright fraudulent.

Many so-called alternative health practitioners have long marketed their own versions of immune therapy based more on belief than evidence. One of Seattle's most celebrated cases of medical negligence involved a physician who in the 1980s and 1990s touted an unproven cancer immune therapy that, according to state officials, led to patient deaths.

Disis, however, is driven solely by the scientific evidence. Within the noise created by the nearly century-old debate between true believers of immunotherapy and those opposing it as dangerous quackery, she began to find some small but promising signals. In the early 1990s, Disis and her colleagues in Seattle were among the first to recognize that breast cancer stimulates an immune response.

Thanks to the work of Disis and others like her, it is now widely accepted that all cancer is immunogenic.

Recently, Disis and UW colleague Vivian Goodell worked with Dr. Nicole Urban at Fred Hutchinson on a study of ovarian cancer funded by the National Cancer Institute and published earlier this month in the Journal of Clinical Oncology.

The Seattle scientists reported that women who happen to have natural immunity to a particular protein, known as p53, also tend to do better against ovarian cancer.

"Several groups are already studying vaccines focused on p53," Disis said. "But many people are still dubious this will really amount to anything."

One form of immunotherapy, though, has already amounted to something.

Many cancer patients today often receive drugs that stimulate an immune response. Interferons and interleukins are cytokines, rapid response proteins produced by white blood cells to attack inflammation, which have been moderately useful against some forms of cancer. Herceptin, used against breast cancer, is a monoclonal antibody -- an artificially produced immune cell designed to attack specific tumors.

What many remain dubious about, Disis said, is the concept of a cancer vaccine. Using these drugs for cancer treatment is known as "passive" immunotherapy because the immune system is boosted temporarily. What Disis is after is "active" immunotherapy, long-lasting immunity similar to that achieved by immunization against infectious diseases.

There are some cancer vaccines in use. The tuberculosis vaccine BCG (Bacillus Calmette-Guerin) is used to treat bladder cancer. The Hepatitis B vaccine and the Human Papilloma Virus vaccine prevent the infections that lead to liver and cervical cancer, respectively. They were all developed as a defense against infectious disease, and happen to prevent cancer, too.

What Disis and her colleagues are trying to do is figure out how the immune system can be similarly harnessed to defend directly against cancer.

It won't be easy. Preliminary results from the breast cancer vaccine study show it did produce an immune response with no evidence of adverse side effects. But nobody's resting comfortably on that finding alone.

Disis believes any effective anti-cancer vaccine will likely have to prompt immunity against multiple proteins and tumor cell types known as antigens in order to create the kind of lasting and effective protection we now get from immunization against infectious disease.

"We're in the process right now of developing a multiple-antigen vaccine for breast and ovarian cancer," she said.

It took a long time to persuade the medical establishment to even consider the immune system as a useful ally in its battle against cancer, Disis noted, but the evidence has piled up. She no longer has to defend her basic assumptions when giving lectures. People are still skeptical about cancer vaccines, she said, but they're listening.

"Now," she said, "all we have to figure out is how to do it."

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