Antigen-Specific Monitoring and Therapy in Pancreatic Cancer

成为公开信息。因此，不包括专有/机密信息。不要超过所提供的空间。 这项建议的主要目标是鉴定人胰腺表达的抗原。 并确认这些抗原是免疫反应的预测因子。这些抗原可以 最终用于靶向癌症疫苗策略。我们一直在开发一种同种异体粒细胞巨噬细胞 巨噬细胞集落刺激因子(GM-CSF)分泌的胰腺肿瘤疫苗途径 胰腺癌患者的治疗。最近完成的第一和第二阶段研究表明， 通过接种后血清GM-CSF水平升高、接种后GM-CSF水平测定该疫苗的生物活性 与系统性疫苗相关皮疹和疫苗召回反应以及疫苗接种后相关的嗜酸性粒细胞增多症 迟发性超敏反应(DTH)对自体肿瘤。这些回应是最多的 常见于无病生存期延长的患者。疫苗接种后免疫效果分析 反应确定间甲硫蛋白和前列腺干细胞抗原(PSCA)为两个候选的新靶点 这两种T细胞反应都是针对保持无病状态的患者。最近完成了一项 切除患者的第二阶段研究，以及目前正在登记的新的第二阶段组合疫苗研究，我们正在 准备扩大我们的免疫目标发现计划，并验证已识别的与免疫相关的基因 免疫反应的靶标。在目标1中，我们将筛选一组早、晚启动的基因 我们治疗的患者免疫的白细胞粘附性淋巴细胞对胰腺癌进展的影响 佐剂II期研究。在目标2中，我们将使用患者验证目标1中评估的一组基因 来自两项疫苗研究的淋巴细胞作为疫苗接种后免疫靶点的相关性。在《目标3》中，我们将 评估AIMS 1和AIMS 2中发现的新抗原靶点的特异性T细胞的功能。我们将集中在 三个功能参数：表达溶解功能、诱导记忆T细胞和诱导更高的 亲和力T细胞。 我们将利用来自临床试验的组织和Core 2来翻译在 拟议的项目3C(前身为2A)用于临床试验监测和新试验，以优先处理候选抗原 在拟议项目1B中进行基础研究，并在拟议项目2B中应用宿主免疫反应的措施。

become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. The broad objective of this proposal is to identify antigens expressed by human pancreatic adenocarcinomas and validate these antigens as predictors of immune response. These antigens can ultimately be used in targeted cancer vaccine strategies. We have been developing an allogeneic granulocytemacrophage colony-stimulating factor (GM-CSF) secreting pancreatic tumor vaccine approach for the treatment of patients with pancreatic cancer. Recently completed phase I and II studies demonstrated the bioactivity of this vaccine as measured by elevated post-vaccination serum levels of GM-CSF, post-vaccination eosinophilia that is associated with systemic vaccine related rashes and vaccine recall reactions, and postvaccination delayed type hypersensitivity (DTH) reactions to autologous tumor. These responses are most often observed in patients demonstrating prolonged disease-free survival. Analysis of post-vaccination immune responses identified mesothelin and prostate stem cell antigen (PSCA) as two candidate new targets against which both T cell responses were directed in patients who remain disease-free. With a recently completed phase II study in resected patients, and a new currently enrolling phase II combinatorial vaccine study, we are poised to extend our immune target discovery program and to validate identified genes as immune relevant targets of the immune response. In Aim 1, we will screen a panel of genes that are turned on early and late in pancreatic cancer progression using immunized leukopheresed lymphocytes from patients treated in our adjuvant phase II study. In aim 2, we will validate the panel of genes evaluated in aim 1 using patient lymphocytes from two vaccine studies for their relevance as post-vaccination immune targets. In aim 3, we will evaluate the function of T cells specific for new antigenic targets identified in aims 1 and 2. We will focus on three functional parameters: expression of lytic function, induction of memory T cells, and induction of higher avidity T cells. We will utilize tissues from clinical trials and Core 2 to translate expressed marker antigens found in proposed Project 3C (formerly 2A) to clinical trial monitoring and new trials, to prioritize candidate antigens for basic studies in proposed Project 1B, and to apply measures of host immune responses in proposed Project 2B.