It’s the “Holy Grail” of prostate cancer, or any cancer, for that matter. A vaccine — perhaps one highly personalized, made from your own cells — that works the way nature intended, only better. There are no side effects; like a body builder, the vaccine add sheft to your immune system. One day such a vaccine may even prevent prostate cancer altogether.

We’re not there yet, but we’re getting closer. Over the last decade, scientists at the Brady Urological Institute, led by Ronald Rodriguez, M.D., Ph.D., have made remarkable progress in this area, diligently over-coming obstacles that at first seemed impossible (for more on hiswork, see story). In the news recently has been widespread coverage of a vaccine called Provenge, given to men with advanced prostate cancer, and reported to prolong their lives. Provenge is made up of a patient’s own blood cells, enriched by immune system cells specially engineered to kill cells that make an enzyme called acid phosphatase.“This is an earlier vaccine,” comments Mario Eisenberger, M.D., R. Dale Hughes Professor of Oncology and Urology, who has designed and tested many prostate cancer drugs, and who recently reviewed this study. More recent vaccines have been targeted to more specific targets, such as PSA or PMSA (prostate membrane-specific antigen, a protein that’s made on the surface of prostate cells). Unfortunately, he notes, acid phosphatase is expressed ubiquitously in tissues throughout the body. “We would not expect a vaccine generated against a generalized protein to be so powerful.”

As it turns out, Eisenberger adds, the key to these results has much to do with the study itself. “The study was originally designed to look at men who had metastatic prostate cancer and who had failed hormonal therapy, to determine whether treatment delayed progression of the disease.Unfortunately,” he says, “it didn’t cause a delay. There was no significant difference in the time it took cancer to progress — which means that the primary end point of the study was negative.”

However, surprisingly, the men who hadrandomly been assigned to the vaccinegroup survived four months longer thanmen who were treated with placebo. “Howcould that be? How could there be a survivaladvantage, if the vaccine failed to preventprogression of the disease?” The answer tothe question may be in understanding whatelse these men received. In all of the men —those who received the vaccine, and those inthe placebo group — cancer progressed.When this happened, the men in the placebo

group were treated with the vaccine. The men who had already taken the vaccine were immediately given the chemotherapy drug taxotere — “a drug of great promise,”says Eisenberger, who has studied taxotere extensively, by itself and in numerous combinations with other drugs, and who will be leading a global study of the drug (see story). Eisenberger and other scientists have reported that giving taxotere plus prednisone prolongs life in men with advanced prostate cancer. Thus, what helped these men the most — getting the vaccine, or receiving effective chemotherapy as soon as the cancer progressed?

Finally, this study was limited by its smal lnumber of participants — only 127 men.With this type of study, the larger the number, the more helpful the results, notes Eisenberger. For example, in one study oftaxotere plus prednisone, published in the New England Journal of Medicine, 1,006 patients were required to show the effect on survival. The company that makes provenge has now embarked on a larger study in an attempt to confirm these results, and clarify the value of this vaccine.