Feb. 5 —  A genetically engineered vaccine that activates the patient’s own immune system to attack and destroy tumors is showing promise for the treatment of prostate cancer. More importantly, the novel strategy holds the potential to stop the spread of all types of cancer, researchers say.

THE CONCEPT IS SIMPLE: Use the body’s own disease-fighting soldiers — so-called killer T-cells — to attack a tumor. Early results show the tactic is working.
       In a preliminary trial of the so-called dendritic cell vaccine in 13 patients with prostate cancer who had exhausted all the usual life-extending treatments, there were no adverse side effects.
       Additionally, immunological testing indicated that the vaccine revved up the patient’s immune system to fight the cancer, says Dr. Johannes Vieweg, an associate professor of urology and assistant professor of immunology at Duke University Medical Center in Durham, N.C., and senior investigator of the study.
       And while this just-published work was done in prostate cancer patients, similar results have since been observed in kidney cancer patients as well, Vieweg says.
       In fact, this approach “extends the scope of vaccination to virtually every cancer patient, regardless of his type of tumor or its genetic makeup,” he adds.
       
WAVE OF FUTURE
       As many in the field believe, targeted vaccines appear to be the wave of the future.
       Dr. Michael Gordon, an oncologist at the Arizona Cancer Center in Tucson, calls them a “huge leap beyond other types of cancer vaccines, which had shown no clinical benefits.”
       What is particularly exciting, Gordon says, is that the vaccines can be customized to each patient and his or her particular type of cancer.
       “We’re very excited,” he says. “Such targeted therapies are the future of cancer treatment.”
       The strategy grew out of a new understanding of how our immune systems react to cancer cells. While the immune system exists, in essence, to recognize outside invaders and attack them, it often has trouble distinguishing normal cells from cancerous ones since both arise from our own tissue.

       Tumor cells are tricky, and have found ways of hiding their abnormal surface proteins — making themselves, in effect, nearly invisible to the immune system, says Dr. Lawrence Fong, a cancer researcher at Stanford Medical School in Palo Alto, Calif., whose work on dendritic vaccines is considered seminal.
       But in recent years, researchers realized that they could take advantage of genetic engineering to wake up a slumbering immune system to the fact that tumor cells have invaded the body.
       Once they recognized the cancer cells as the enemy, the immune system’s T cells would do their job — and attack, they reasoned.
       And they were right.
       
NOVEL APPROACH
       In the latest approach, a team led by Vieweg took advantage of a rare but integral part of the immune system known as the dendritic cell. A dendritic cell is a type of white blood cell that activates the immune system by capturing antigens — substances that trigger immune responses against viruses, bacteria and tumors — and presenting them to T-cells.
       

To create the vaccine, genetic engineering was employed to fuse immature dendritic cells with RNA from prostate-specific antigen (PSA) from the same patient. PSA is a protein that is secreted by the prostate gland and is often elevated in prostate cancer. The hybrid was then injected back under the patient’s skin as well as intravenously.
       In the trial, 13 men with prostate cancer that was continuing to spread despite standard treatment with hormones were given three escalating doses of the vaccine.
       The results were published in the February issue of the Journal of Clinical Investigations.

       Overall, the vaccine was well-tolerated. Four subjects developed low-grade fevers and flu-like symptoms, and four patients had inflammation at the site of the injection that subsided after two to three days.
       The researchers then performed immunological tests to ensure that T-cells were functioning and able to kill tumor cells, in addition to tests to determine whether the T-cell levels rose.

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       In all 13 participants, the researchers detected a dramatic increase in PSA-specific T-cells, suggesting the vaccine was successful in boosting the immune system and turning T-cell attention to the cancer at hand.
       A second test showed that these T-cells can actually kill tumor cells, he adds. “We took T-cells from the patient and incubated them with tumor cells and showed killing in the test tube,” he says.
       Simply showing an increase in number of T-cells doesn’t prove the immune system is actively attacking the tumor, but this latter test does, Vieweg explains.
       Immunological data, which is sometimes not collected in such trials, is highly important in proving that the cancer vaccine is working in the patient and other influences are not at work, according to Vieweg.
       “Some studies examine only if there is a reduction in tumor growth, but this would only show part of the story,” he said. “You wouldn’t see the changes in the body that might indicate that a vaccine is promising.”
       The Duke study was not designed to determine whether cancer was eradicated, but a “little impact” was seen, he says. In six of seven patients, PSA progression was slowed. (The other six patients were excluded from this part of the analysis because they underwent additional treatments that could impact PSA levels.)
       “In patients with disease so advanced, to see any effect on PSA is huge,” Vieweg says.
       The next step for prostate cancer, Vieweg says, is to give the vaccine to patients who have just had their prostates removed but in whom some lingering cancer cells remain.
       “Since the disease is at a much earlier stage, we expect we will see an actual lowering of PSA levels as well as better control of cancer cells,” says Vieweg, adding that he just got official approval for such a study.
       
BRANCHING OUT
       In the meantime, though, Vieweg isn’t sitting still. He’s already branched out and has just completed a study of a more potent version of his vaccine in patients with kidney cancer.
       The idea, he says, is to use fully mature dendritic cells and program them to carry multiple tumor antigens rather than just PSA. This involves using RNA from the whole tumor — rather than from PSA or another cancer antigen — to create the vaccine.
       While Vieweg is not free to share the details of the kidney cancer trial pending publication in a medical journal, “the results were very interesting, very encouraging,” he says.
       Eventually, he hopes the approach will prove successful for all types of cancer. Meanwhile, other researchers are employing similar strategies; in May, for example, Fong reported early success with another type of dendritic vaccine in colorectal and lung cancer patients.
       “The beauty of all these approaches is that the vaccines boost the immune system, rather than beat it up like chemotherapy,” Vieweg says.
       And use of RNA from the whole tumor will make them far more user-friendly — helping cancer patients regardless of what type of tumor or genetic makeup.