IMMUNOLOGIC THERAPY OF PROSTATE CANCER

点击翻译按钮获取中文摘要

Prostate cancer is currently the commonest cancer in men. Sixty percent of new cases at the time of diagnosis are not organ confined. Once prostate cancer is far advanced, the impact of therapy has been marginal. Additional methods to intervene therapeutically in advanced disease are needed. One potential novel intervention would be T cell vaccines and/or T cell therapy directed against prostate specific antigens. There is increasing evidence, that there is an existent immune response to cancer in many patients and that some of the antigens recognized by autologous B cells and T cells are diffentiation antigens. What remains to be determined is whether immune responses against diffentiation antigens can be manipulated to confer protection against the cancer. A major theoretical problem with targeting T cell therapy against differentiation antigens is that eliciting or boosting such immunity can result in destructive autoimmunity. However, if autoimmunity is elicited against tissues with dispensable function, (i.e., the prostate gland in patients with prostate cancer), the destructive autoimmunity might eradicate cancer cells originating in the nominated tissue. Others have shown that immunizing rodents to homogenate prostate tissue can induce T cell mediated autoimmune prostatitis. However, the target antigens are unknown, and the autoimmunity has been observed to be self limited. Issues that need to be elucidated before attempting to develop the use of autoimmune prostatitis as therapy in humans for prostate cancer include: 1) which prostate- specific proteins can serve as targets for T cell attack, 2) how to prospectively and effectively circumvent tolerance to prostate self proteins, and, 3) how to sustain the destructiveness of autoimmune prostatitis. Current grant proposes to examine these issues in a rat model. The prototype antigen selected for study is prostatic acid phosphatase (PAP), a known tumor marker for human prostate cancer. Rat PAP, a 50kD secreted glycoprotein made exclusively by prostatic epithelial cells, is 79 percent homologous to human PAP. Thus, principles elucidated in the rat model might be applicable to the human situation.