Adenocarcinoma of the prostate is the most common malignancy in men. In patients with disseminated, hormone refractory disease, treatment is palliative and does not prolong survival. The applicant proposes to develop and evaluate an immunotherapeutic approach to prostate cancer that utilizes dendritic cells (DC) pulsed with prostate acid phosphatase (PAP), a well characterized prostate antigen. DC are extremely potent antigen presenting cells, capable of sensitizing naive T lymphocytes to protein antigens and eliciting potent immune responses, in vitro and in vivo. The applicant has developed methods for obtaining DC from human peripheral blood and demonstrated that these cells, but not monocytes, can sensitize naive CD4+ and CD8+ T cells to nominal antigens, in vitro. Recently, the applicant's group has demonstrated in four patients with advanced malignant B cell lymphoma that administration of tumor antigen pulsed DC is well tolerated, induces antigen-specific T cell responses and (in two patients) tumor regression. In the proposed studies the immunogenicity of PAP pulsed human DC will be analyzed in vitro, the immunogenicity, toxicity and anti-tumor effects of PAP pulsed rat DC will be analyzed, in vivo, in rats inoculated with the Dunning tumor line, and the immunogenicity and toxicity of PAP pulsed DC will be analyzed in patients with disseminated carcinoma of the prostate. The results of these studies should indicate whether DC based immunotherapy has a potential role in the treatment of prostatic cancer.
