How Close Is a Breast Cancer Vaccine, Part 2

Dr. Mary L. Disis and colleagues at the University of Washington decided to test an HER-2/neu vaccine after discovering that some breast cancer patients already have a low level of immunity to the protein. They hypothesized that a vaccine might significantly bolster this existing immunity and, in turn, induce an anticancer effect.

“This is one of the first trials to show that it’s possible to generate an immune response to a cancer protein by immunizing patients with fragments of the [same] protein,” said Disis, who presented her findings recently at the Era of Hope breast cancer conference in Atlanta, Ga. The meeting is sponsored by the U.S. Department of Defense’s breast cancer research program. “It is also the first step toward the long-term goal of developing an affordable and hopefully practical vaccine to prevent cancer recurrence.”

Disis explained that the study she is overseeing is designed to test the vaccine’s safety and its ability to trigger an immune system response. Ultimately, of course, it is the immune system and not the vaccine that acts against the development of cancer.

Unlike previous anticancer vaccines, this one targeted against HER-2/neu stimulates the immune system’s helper T-cells. Helper T-cells are important because they spur the production of other immune system components to attack and destroy invaders. The vaccine thus is innovative because previous vaccines have concentrated on stimulating another type of T-cell in the immune system, the so-called killer cell. With a helper T-cell in force, a stronger overall attack can be mounted.

Disis initially tested the vaccine in 64 volunteers, all of whom had completed treatment for stage 3 or stage 4 breast cancer, as well as ovarian and lung tumors. Each patient, who agreed to long-term follow-up, received six vaccinations.

“These follow-up data suggest that the immune system may be able to ‘remember’ and respond to the protein long after vaccination has taken place — the hallmark of a successful vaccine,” Disis said.

But just as there are different forms of chemotherapy, there is more than one way to approach a breast cancer vaccine. Researchers at Memorial Sloan-Kettering Cancer Center are focusing on a protein known as MUC-1, which is produced by patients with breast, ovarian and pancreatic cancers. At Sloan-Kettering, MUC-1 is mixed with two unusual substances. One is KLH — keyhole limpet hemocyanin, — a shellfish compound; the other is QS21, an extract from bark common to a South American tree. These two substances are added to the vaccine because they have been shown to elicit a strong immune response.

Patients are to receive five vaccinations in a variety of doses to determine which causes the strongest response with the least number of side effects. The hope is to keep metastatic breast cancer at bay.

In an animal study reported at the Era of Hope meeting, scientists at the University of Michigan found that significant regression of breast tumors occurred in mice treated with yet another type of anticancer vaccine. In a study led by Dr. Christopher Kirk, mice were injected with dendritic cells, which are known to be potent immune system stimulants because they trigger the production of killer T-cells.

Dendritic cells can act as scavengers, devouring tumor cells that are dying as a result of apoptosis, or programmed cell death. After that meal, dendritic cells are able to present pieces of the digested tumor proteins to T-cells, and this is what causes the immune response.

Once T-cells see the snippets of tumor proteins, they multiply and attack the entire tumor.

Kirk and colleagues injected dendritic cells directly into the tumors of 25 mice and were able to see complete tumor regressions in five of the 25 treated mice. These tumors stayed in remission for more than three months and new cancers grafted into the same animals did not grow, strongly suggesting that killer T-cell response remained high. In the remaining mice, the treatment reduced tumor growth by two-thirds when compared with control mice. The controls did not receive the dendritic treatment.

“The next step is to find the best way of translating these findings into a human clinical trial,” said Kirk, a research fellow in the Tumor Immunology Program at the University of Michigan.

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