Research Sets Stage for Possible Autoimmune Therapy

BUFFALO, NY--Autoimmune prostatitis has been suggested as a new method for treating prostate cancer, and prostate-specific proteins are currently being sought to serve as targets for an autoimmune attack that could offer therapeutic benefits in prostate cancer.

"Autoimmunity can destroy normal or malignant prostate tissue," said Martin A. Cheever, MD, director of Medical Affairs, Corixa Corporation, and clinical professor of medicine, University of Washington, Seattle. "One problem, however, is that a typical autoimmune response in not fast enough to eliminate a tumor," he added.

Speaking at the first meeting of the Regional Cancer Center Consortium for Biological Therapy of Cancer, hosted by Roswell Park Cancer Institute, Dr. Cheever said that the initial studies attempted to narrow the field of study and determine the principles of autoimmune prostatitis therapy.

The first study involved rats inoculated with prostate acid phosphatase (PAP). These animals exhibited antibody and T-cell immunity to PAP, without prostate inflammation or destruction, Dr. Cheever reported.

The next step was to inoculate rats with a grouping of all rat prostate proteins. These animals exhibited a dominant immune response to one protein, determined to be prostatic steroid binding protein (PSBP), but also wtihout any prostatitis.

Response to Purified PSBP

In a follow-up study, rats who received purified PSBP finally exhibited the response that was anticipated. "We found vigorous antibody and T-cell response, marked prostate inflammation, and destruction of prostate tissue in some, but not all, of the rats inoculated with purified PSBP," Dr. Cheever said.

In follow-up work, the investigators found they could consistently generate rapid and severe destructive autoimmune prostatitis using a therapy of T cells immune to PSBP. "These tests showed that T-cell therapy is substantially more effective than vaccine therapy with these antigens," he said.

Prostatic steroid binding protein is the immunodominant protein in the rat prostate, he said. The finding that T cells would react with a common protein was surprising, Dr. Cheever commented, since immunologic tolerance is considered to be proportional to the level of expression.

"Thus, we had not expected that a strong immune response would be generated against such an abundant self-protein. These results strongly imply that PSBP, an apocrine-secreted protein, is well sequestered from the immune system under normal conditions," Dr. Cheever said.

He noted that his lab has not yet been able to clone the human homologue to rat PSBP, but he noted that other human prostate proteins should be able to serve as targets for immune attack by vaccines.

Human Prostate Proteins

Dr. Cheever said that several groups of patients are being studied to find such human prostate proteins:

1. Patients with granulomatous prostatitis (rock hard prostate).

2. Patients who present with an elevated prostate-specific antigen (PSA) measurement with evidence of inflammation on biopsy.

3. Patients immunized to self-prostate and self-prostate cancer.

4. Patients with prostate cancer and a confirmed immune response to proteins expressed by autologous cancer.

"We are examining data from all four groups, hoping to find a unique protein that we can use to mimic the destructive prostatitis that we were able to induce in the rat model," Dr. Cheever said. "I expect that the fourth group of patients will be the most valuable."