Immunotherapy Slows Progression of Prostate Cancer

November 30, 2000
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New therapy that employs the immune system to attack and kill prostate cancer cells slowed the disease progression in some men and decreased levels of prostate specific antigen (PSA), a protein in the blood that often indicates prostate cancer, a UCSF study has found.

The study of 31 men involved collecting patients' dendritic cells - an integral part of the immune system -- from the bloodstream and mixing them in test tubes with a synthetic version of prostatic acid phosphatase (PAP), an antigen found on the surface of most prostate cancer cells. Dendreon Corp. in Seattle Washington prepared the therapy, called Provenge, made of synthetic PAP combined with dendritic cells.

The modified dendritic cells were then infused back into the patient with the hope that they would help trigger the patient's immune system to kill prostate cancer cells throughout the body, said Dr. Eric Small, an oncologist at UCSF Medical Center and a member of the UCSF Helen Diller Family Comprehensive Cancer Center's Urologic Oncology program.

The results were published in the Dec. 1 issue of the Journal of Clinical Oncology.

Dendritic cells scavenge foreign material, such as bacteria and viruses, and then interact with another important component of the immune system, lymphocytes, bringing this foreign material to the lymphocytes' attention. The lymphocytes then jump into action and circulate through the body, destroying the foreign substance. The goal of the study was to see if these modified dendritic cells would train the lymphocytes to recognize cells with PAP on their surface as a foreign substance and kill those cells. The men in the study received an infusion of dendritic cells once a month for three months.

The Phase I and II study enrolled men with advanced prostate cancer - defined as tumors spreading beyond the prostate to other parts of the body and no longer responding to conventional hormone therapies. The median age of the participants was 69, with a range from 48 to 83. Twenty of the men had a strong immune response to PAP after treatment. For these men, time until their disease progressed, or became worse, was 34 weeks compared to 13 weeks for those patients who had weaker immune responses.

In addition, three patients had a greater than 50 percent decrease in PSA. Three more patients had a 25 percent to 49 percent decrease in PSA. A PSA decrease of more than 50 percent has been accepted by most researchers as a reasonable indication of anticancer activity, according to the study.

Small said the results of this study were encouraging. "It really shows the immune system can be manipulated and made to recognize prostate cancer," he said. "This trial shows we can break tolerance to the antigen. Immunologically, we always thought we couldn't do that in prostate cancer."

While other studies have shown immunotherapy to have some benefit in melanoma and kidney cancer, this study is one of the first to demonstrate an effect in prostate cancer, Small said. "Immune therapy for prostate cancer has not historically been viewed with much enthusiasm. This is because it was believed that the immune system, for whatever reason, did not recognize prostate tumors as foreign and therefore they did not illicit an immune response," Small said. "As it turns out, that isn't the case. Apparently, the immune system was just not being adequately stimulated to attack the cancer."

The therapy was well tolerated by patients, with mild fever being the most common side effect. The trial lays the groundwork for future research of this therapy. Small is principal investigator of a Phase III trial of Provenge that is enrolling about 240 men with advance disease at multiple sites nationwide.

Prostate cancer is the most common cancer, excluding non-melanoma skin cancers, in American men, according to the American Cancer Society, which estimates that 180,400 new cases of prostate cancer will be diagnosed this year in the United States and about 31,900 men will die of this disease. It is the second leading cause of cancer deaths in men, exceeded only by lung cancer.

Physicians initially treat advanced disease by prescribing hormones to deprive a man's body of testosterone, which fuels prostate cancer growth. However, all patients ultimately develop hormone independent disease, meaning the cancer progresses despite lowering testosterone. The median survival for this group of patients is about a year, according to the study. Dendreon funded this study and is funding the Phase III trial.