A PILOT PHASE IB TRIAL OF A PSA PEPTIDE VACCINE

描述：（申请人的描述） 前列腺癌表达组织特异性分化抗原， 能够靶向高度选择性自身免疫T细胞免疫应答， 消除恶性转化细胞的能力。 的目的 目前的研究是确定是否合成肽对应于 前列腺特异性抗原内确定的T细胞表位能够引起 局部晚期或转移性，激素- 敏感性前列腺癌 具有高亲和力的九聚体PSA肽， HLA-A2和引发HLA-A2限制性T细胞的能力将用于 对复发风险高的局部晚期肿瘤患者进行免疫接种， 前列腺敏感性转移癌。 该提案涉及 假设PSA肽与自体树突细胞或 一种旨在促进树突状细胞成熟和体内功能的佐剂 将诱导肽特异性T细胞，并将介导有效的抗肿瘤 方面的影响. 该提案的具体目标是：1）确定能力 PSA-肽疫苗接种诱导或增强短期和长期PSA- 特异性T细胞免疫（细胞溶解、增殖、细胞因子释放）， 前列腺癌患者; 2）为了确定PSA-肽- 前列腺癌患者接种疫苗以诱导或增强 细胞溶解性T淋巴细胞（CIL）能够溶解HLA-A2+肿瘤， 内源性表达PSA蛋白; 3）确定临床病程 在B2/C或D1/D2期激素接种疫苗的患者中， 敏感性前列腺癌;以及4）确定 在基于PSA-肽的治疗后表现出临床进展性疾病 疫苗接种在其进行性癌症中产生PSA-或HLA-A2-缺失变体 作为免疫逃逸和疾病进展的潜在机制。

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.