Phänotypische und funktionelle Charakterisierung von zytotoxischen T-Lymphozyten gegen Melanom-assoziierte Antigene bei gesunden Individuen und bei Melanompatienten vor und nach Peptidvakzinierung

健康个体和黑色素瘤患者在肽疫苗接种前后针对黑色素瘤相关抗原的细胞毒性 T 淋巴细胞的表型和功能特征

• 批准号: 5290838
• 负责人: Professor Dr. Alfred Zippelius
• 金额: --
• 依托单位: Abteilung für Onkologie
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5290838?language=en
• 关键词: Ph; notypische; und; funktionelle; Charakterisierung

Powerful systemic and local T cell based immune responses against melanoma-associated antigens have been repeatedly identified in humans. New developments now greatly facilitate the analysis of tumor-specific cytotoxic T cells (CTL), although detectable immune responses are rarely sufficient to arrest tumor growth as apparent by the grim prognosis of advanced melanoma. Furthermore, very little is known about distinct phenotypes of CTL that have recently been found in melanoma patients and even healthy individuals. In the first part of the proposed work, the applicant will phenotypically and functionally characterize T cells reactive against the self-antigen Melan-A/MART-1 that are detectable at high levels in two thirds of normal HLA-A2 healthy blood donors. In the second part, the different functional stages of CTL in sentinel lymph nodes and peripheral blood specimens of melanoma patients before and after peptide-based vaccination will be studied. Taken together, the proposed work will provide important information in our understanding of the dynamics of the specific CTL response to tissue-specific self antigens under both physiological and pathological circumstances and will help to improve the design of specific immunotherapeutical approaches to cancer.

针对黑素瘤相关抗原的强大的基于全身和局部T细胞的免疫应答已在人类中反复鉴定。新的发展现在大大促进了肿瘤特异性细胞毒性T细胞（CTL）的分析，虽然可检测的免疫反应很少足以阻止肿瘤生长，因为晚期黑色素瘤的预后很差。此外，很少有人知道最近在黑色素瘤患者甚至健康个体中发现的CTL的不同表型。在拟议工作的第一部分中，申请人将在表型和功能上表征对自身抗原Melan-A/MART-1具有反应性的T细胞，这些T细胞在三分之二的正常HLA-A2健康献血者中可检测到高水平。在第二部分中，将研究基于肽的疫苗接种前后黑色素瘤患者的前哨淋巴结和外周血标本中CTL的不同功能阶段。两者合计，所提出的工作将提供重要的信息，在我们的理解的动态的组织特异性自身抗原的特异性CTL反应的生理和病理情况下，将有助于改善设计的特异性免疫治疗癌症的方法。