This report originally appeard on the Sapient Health Network web site, which later became WebMD.

Testing of Prostate Cancer Vaccine Moves Forward

Beginning this summer, patients with advanced prostate cancer may be able to try treatment with a cancer "vaccine" at several leading cancer centers. The announcement of plans to expand trials of immunotherapy for prostate cancer was made at the 1998 American Cancer Society Science Writers Seminar. 

Dr. Gerald Murphy of Northwest Hospital in Seattle, Washington reports that in the first round of tests, 9 out of 33 prostate cancer patients saw their PSA levels drop by 50 percent or more, along with improvements on bone scans and other measurements. In another 11 men, the cancer neither advanced nor retreated. All the men have advanced disease that no longer responds to hormone treatment. Dr. Murphy says that while they had an expected survival of only six months, some of the partial responses have lasted longer than a year. 

"That's extremely encouraging," says Dr. Murphy. "That the results were there was cause for happiness, but that they were durable and sustainable after the infusions, for a significant period of time... suggests that the immune system can be helped, that at least for a while that they can restore order, and for a period of time battle the odds." 

Now other research teams will try to duplicate, and perhaps build on, the early success. The five centers that plan to begin tests this summer are Cedars-Sinai/UCLA in Los Angeles, St. Luke's Medical Center in Milwaukee, Wisconsin, M.D. Anderson Cancer Center in Houston, Texas, Memorial Sloan-Kettering Cancer Center in New York City, and the University of Michigan Medical Center in Ann Arbor. 

Dr. Murphy says he and his colleagues turned their efforts toward bolstering patients' immune systems for a simple reason: if prostate cancer returns after initial treatment, there is very little doctors can now offer their patients. "We sought immune approaches because all of our traditional efforts, while successful, there's a percentage of every one of them that doesn't succeed. And that there's a significant number of men who, after having had successful surgery or radiation or seed therapy, and after hormones, chemotherapy or radiation, the disease is still progressing." 

In theory, the immune system should naturally recognize cancer cells as disease and then destroy them; but sometimes the body's defenses fail. Dr. Murphy points out that as we age, our immune system gets weaker. What's more, cancer cells have ways to hide from the immune system. This immunotherapy approach attempts to address both problems, by growing additional immune cells, and by attempting to "un-mask" prostate cancer cells. 

The first half of the strategy involves filtering a specific type of immune cell out of the patient's blood. These dendritic cells, as they are called, are part of the immune system's advance scout teams. In the laboratory, scientists can help the dendritic cells multiply, until millions of them are ready to being infused back into the patient's blood. 

But the strategy appears to work best when the dendritic cells are given the "scent" of prostate cancer cells. To do that, researchers first had to identify some unique identifying feature of the cancer. 

"What we have done is identify a unique antigen that's present on the surface of prostate cells that increases, or is so-called 'up-regulated' in the presence of cancer, and just goes bananas in the presence of a failure to respond, or hormone resistance," says Dr. Murphy. 

The feature researchers homed in on is part of the system that prostate cancer cells use to feed their explosive growth. Dr. Murphy points out that cancer cells have huge nutritional needs, because their metabolism works 100 times the rate of normal cells. As a result of this voracious appetite, the surface of a prostate cancer cell is studded with abnormally high amounts of a substance called PSMA. "These PSMA, prostate specific membrane antigen," he says, "that has so much of its structure outside of the cell, and a 'pipe' going through the membrane to the inner workings, this is the pipe that conducts a certain amount of the essential nutritional products to the cell." 

So the second part of the experimental therapy involves mixing PSMA with the dendritic cells. In the first tests, researchers used two fragments of the protein molecule. The next round of tests will use a purified form of whole PSMA. It is precious material. Producing just five grams cost more than $1-million. But a little goes a long way. Dr. Murphy says the total cost of treatment so far is about $10-thousand per patient; not cheap, but in line with many other therapies. 

According to Dr. Murphy, the dendritic cells that have been primed with PSMA are then ready for action, once they are re-infused into the patient. "We expose them to this unique antigen in the test tube, so that they can be ready," he says. "And then when we put them right back in the blood stream, they go right back to their colleagues and friends, the T-cells, and say, "Hey, look what I've seen." Once those T-cells get that message, they are able then to either help kill or kill directly a prostate cancer cell with that antigen on it." 

The strategy does not always work. Cancer cells can sometimes mutate to hide antigens or take other measures to thwart the immune system. But Dr. Murphy says the fact that even a few patients have responded in the first two rounds of experiments is a significant advance. 

Perhaps just as important, especially for men who have already endured difficult prostate cancer treatments, this immunotherapy seems to have few, if any, side-effects. "And that's what's so nice," says Dr. Murphy, "because having to have additional treatments, if you've been through surgery and radiation, and hormone treatment, chemotherapy, yet another hurdle, this is very good news to the prostate cancer patient." 

The multi-center trial will assign patients to one of five variations of the immunotherapy: 

• intravenous infusion of the PSMA antigen, 
• injection of PSMA into the skin (where a special type of immune cell is found,) 
• infusion of dendritic cells primed with PSMA, 
• dendritic cells, PSMA, and a substance called GM-CSF that boosts immune cell production, 
• or dendritic cells, PSMA, and another immune system growth factor called Flt-3.

While the multi-center trial will enroll men with advanced prostate cancer, Dr. Murphy and his colleagues at Northwest Hospital are already testing the treatment on men much earlier in the course of their disease. These men have rising PSA levels, but no other symptoms, after initial treatment. While they do not have widespread disease, the rising PSA indicates that surgery or radiation failed to remove or kill all the patient's prostate cancer cells. Early results from this trial may be available this summer.  Since standard therapy has little to offer men with metastatic prostate cancer, any new option is welcome, but Dr. Murphy stresses that these trials are just the initial steps toward effective immunotherapy of prostate cancer.