UCLA Starting Clinical Trials Of Immunological Approach

A team of UCLA research physicians at the Jonsson Comprehensive Cancer Center and the Clark Urology Center has discovered a new way to inhibit the growth of prostate cancer cells and reduce their potential for spreading to other parts of the body.

Based on the findings, UCLA is starting a clinical trial in which immunotherapy for the first time is being administered to patients with prostate cancer, said Dr. Arie Belldegrun, chief of genitourinary oncology in the Division of Urology at the UCLA School of Medicine, where he is a full professor.

The findings were described by Belldegrun and his colleagues in the May 1 issue of the journal Cancer. Belldegrun is a member of the Jonsson Comprehensive Cancer Center at UCLA and was the principal investigator for the study.

"This is a thoroughly comprehensive study exploring the use of immunotherapy to treat human prostate cancer," said Dr. Mitchell Sokoloff, first author of the paper and chief resident in the Division of Urology at UCLA.

Belldegrun noted that, with immunotherapy, "we trick the body into looking at certain cells as foreign objects to be rejected, much as one might fight off a viral infection. In our laboratory, we developed a way to destroy some prostate cancer cells and induce alterations in other prostate cancer cells. Those alterations not only slow the growth of the cells, but also reduce their potential to spread to other parts of the body. These are really very exciting results."

To get those results, Belldegrun treated prostate cancer cells in the laboratory with certain proteins. The proteins, called cytokines, are hormone-like substances that regulate the human immune system. They act as signaling devices that turn on the immune system when required to fight off a disease or infection.

One anticipated problem with cytokine immunotherapy for prostate cancer is the side effects of injected cytokines. When injected intravenously, they can cause reduced blood pressure and flu reactions that can be life-threatening.

"To overcome this problem, we are injecting cytokines directly into the prostate tumor," Belldegrun said. "In this way we can give much smaller doses of cytokines, thereby avoiding systemic side effects, although there is the possibility of minor local side effects that would not be life-threatening."

Surgery and radiation are effective treatments for prostate tumors that are detected early on. "But the common treatment for advanced prostate cancer is to deprive the tumor cells of male hormones," Sokoloff said. "That treatment is usually effective for between three and five years. Then the cancer becomes hormone-resistant, and we are left with no effective treatment."

After completion of clinical trials involving both immunotherapy and surgery, the first of which is under way at UCLA, Belldegrun foresees attacking prostate cancer with a combination of immunotherapy and other treatments such as surgery and radiation, much as is done now for kidney cancer.

"Based on the data described in our paper, I think that within two or three years immunotherapy will be an accepted method of fighting prostate cancer," Belldegrun said. "Our success with cytokines used in the lab to fight prostate cancer cells bodes well for our current clinical trial with humans. This approach may also serve as the basis for future gene therapy using genetically engineered tumor cells to produce these very same cytokines." [Contact: John Dreyfuss]

(Editor's Note: Persons wishing to be considered for acceptance in the UCLA clinical trial should call 310-206-1434.)

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