A PILOT PHASE IB TRIAL OF A PSA PEPTIDE VACCINE

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DESCRIPTION: (Applicant's Description) Prostate cancers express tissue-specific differentiation antigens that might be able to target highly selective autoimmune T cell immune responses with the ability to eliminate malignantly transformed cells. The purpose of the current study is to determine whether a synthetic peptide corresponding to a defined T cell epitope within prostate-specific antigen is able to elicit anti-tumor immunity in patients with locally advanced or metastatic, hormone- sensitive prostate cancer. A nonameric PSA peptide with high affinity for HLA-A2 and the ability to elicit HLA-A2 restricted T cells will be used to immunize patients with locally advanced tumors at high risk of recurrence or hormone-sensitive metastatic prostate cancers. The proposal addresses the hypothesis that a PSA peptide administered with autologous dendritic cells or an adjuvant designed to promote dendritic cell maturation and function in vivo will induce peptide-specific T cells and will mediate potent anti-tumor effects. The specific aims of the proposal are: 1) To determine the ability of PSA-peptide vaccinations to induce or enhance short- and long-term PSA- specific T cell immunity (cytolytic, proliferative, cytokine release) in prostate cancer patients; 2) To determine the ability of PSA-peptide- vaccinations in prostate cancer patients to induce or enhance the development of cytolytie T lymphocytes (CIL) capable of lysing HLA-A2+ tumors which endogenously express PSA protein; 3) To determine the elinical disease course of prostate cancer in vaccinated patients with stage B2/C or D1/D2 hormone- sensitive prostate cancers; and 4) To determine whether patients who demonstrate clinically progressive disease following PSA-peptide based vaccination develop PSA- or HLA-A2- loss variants in their progressive cancer as a potential mechanism of immune escape and disease progression.