IMMUNOLOGIC THERAPY OF PROSTATE CANCER

前列腺癌是目前男性最常见的癌症。 六十 在诊断时，新病例的百分比不是器官局限性。 一旦前列腺癌是远远先进的，治疗的影响已经 边缘。 治疗性干预晚期乳腺癌的其他方法 疾病是需要的。 一种潜在的新干预措施是T细胞 针对前列腺特异性抗体的疫苗和/或T细胞疗法 抗原 越来越多的证据表明， 许多患者对癌症的免疫反应， 自体B细胞和T细胞识别的抗原是分化的 抗原 尚待确定的是免疫反应是否 可以操纵针对分化抗原的抗体以提供保护 对抗癌症 靶向T细胞的主要理论问题 针对分化抗原的治疗是引发或加强这种分化抗原， 免疫可导致破坏性自身免疫。 但如果 针对具有免疫功能的组织引发自身免疫，（即， 前列腺癌患者的前列腺），破坏性 自身免疫可能会根除癌细胞起源于指定的 组织. 其他人已经证明，免疫啮齿动物匀浆 前列腺组织可诱导T细胞介导的自身免疫性前列腺炎。 然而，靶抗原是未知的，并且自身免疫具有 被认为是自我限制的。 需要阐明的问题 在尝试开发自身免疫性前列腺炎的用途之前， 人类前列腺癌的治疗包括：1）前列腺- 特定的蛋白质可以作为T细胞攻击的目标，2）如何 前瞻性和有效地规避对前列腺自身 蛋白质，以及，3）如何维持自身免疫的破坏性 前列腺炎 目前的赠款建议审查这些问题在一个老鼠 模型 选择用于研究的原型抗原是前列腺酸 磷酸酶（PAP），已知的人前列腺癌的肿瘤标志物。 大鼠PAP是一种50 kD的前列腺分泌糖蛋白， 与人类PAP有79%的同源性。 因此，在本发明中， 在大鼠模型中阐明的原理可能适用于人类 形势

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.