A PILOT PHASE IB TRIAL OF A PSA PEPTIDE VACCINE

描述：(申请人描述) 前列腺癌表达组织特异性分化抗原，可能 能够靶向高度选择性的自身免疫T细胞免疫反应 消除恶变细胞的能力。该计划的目的是 目前的研究是确定一种合成肽是否与 前列腺特异性抗原中明确的T细胞表位能够诱导 局部晚期或转移性荷尔蒙患者的抗肿瘤免疫 敏感的前列腺癌。一种对PSA具有高亲和力的非单体PSA多肽 人类白细胞抗原A2和诱导人类白细胞抗原A2限制性T细胞的能力将被用于 为局部晚期肿瘤复发或复发风险较高的患者接种疫苗 激素敏感型转移性前列腺癌。该提案涉及 假设PSA多肽与自体树突状细胞或 一种旨在促进树突状细胞在体内成熟和功能的佐剂 将诱导多肽特异性T细胞，并将介导强大的抗肿瘤 效果。该提案的具体目的是：1)确定能力 接种PSA多肽疫苗以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)测定PSA-肽的能力- 在前列腺癌患者中接种疫苗以诱导或促进发育 细胞溶解T淋巴细胞(CIL)能够裂解人类白细胞抗原A2肿瘤 内源性表达PSA蛋白；3)确定临床病程 接种B2/C期或D1/D2期激素的患者中前列腺癌的风险- 敏感的前列腺癌；以及4)确定患者是否 显示基于PSA多肽的临床进展性疾病 接种疫苗可使进展期癌症患者发生PSA或人类白细胞抗原A2缺失变异 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.