Background: Prostate cancer is a significant cause of morbidity and death worldwide. At present, there is no adjuvant therapy for prostate cancer that can eradicate micrometastatic disease present at the time of initial therapy. Vaccines are particularly appealing for prostate cancer, because an immune response directed at the prostate that could induce a long-lived destructive autoimmune prostatitis might have therapeutic benefit. To date, however, the best target vaccine antigens for prostate cancer have not truly been defined. The identification of antigens that are naturally recognized in inflammatory prostatitis might suggest more appropriate target antigens for prostate cancer vaccines. A rat model for evaluating immunization strategies has been developed targeting a specific antigen, prostatic acid phosphatase (PAP). We have shown that DNA vaccines targeting PAP can elicit antigen-specific immunity and prostate inflammation. In addition, a rat model of autoimmune prostatitis has existed in which rats treated with castration or estrogen develop lymphocyte-mediated tissue inflammation and destruction. The antigen(s) recognized in this model have not been identified. Similarly, it has recently been shown that patients with prostate cancer treated with androgen ablation also develop a CD4 lymphocyte infiltration in normal and malignant prostate tissue. Objective / Hypothesis: The use of androgen deprivation therapy results in prostate antigen-specific immune responses in both patients with prostate cancer and rats, and vaccines directed at these antigens can induce prostate tissue inflammation.
Specific Aims : (1) To identify, in a rat model, the prostate antigen(s) that after treatment with androgen deprivation therapy induce antigen-specific immune responses and prostate tissue inflammation; (2) To identify, in patients with prostate cancer, the prostate antigen(s) recognized after treatment with androgen deprivation therapy. Study Design:
The first aim will identify in a rat model the antigens of the prostate recognized following hormonal therapy, a treatment known to cause prostate tissue inflammation in rats and humans, using a modification of the SEREX technique. A DNA immunization strategy will then be attempted targeting the identified antigens, to determine whether an antigen-specific response to the identified antigens will elicit prostatitis.
The second aim will use the same methods as in Aim 1 to translate these findings to patients with prostate cancer by identifying the antigens immunologically recognized in patients treated with hormonal therapy.
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