PEPTIDE SPECIFIC CD8 T CELLS AS MARKER OF VACCINE ACTION

肽特异性 CD8 T 细胞作为疫苗作用的标记

• 批准号: 2682204
• 负责人: JEAN-CLAUDE BYSTRYN
• 金额: $ 16.23万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2682204
• 关键词: CD8 molecule; MHC class I antigen; cellular immunity; clinical research; clinical trials; cytotoxic T lymphocyte; human subject; human therapy evaluation; humoral immunity; melanoma; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; tumor antigens; vaccine development

DESCRIPTION (Adapted from the Investigator's Abstract): The investigator's goal is to determine whether a novel assay for peptide-specific CD8+ T cell responses to cancer vaccines can be used to evaluate the immunological activity of the vaccines and to predict their clinical effectiveness. This proposal exploits several recent advances in the investigator's laboratory and clinic: 1) the development of a new assay for peptide-specific CD8+ T cells which is sufficiently sensitive to detect vaccine-induced increases in these cells in peripheral blood without the need for in vitro sensitization; 2) the identification of panels of peptides on important melanoma antigens which are recognized by human CD8+ T cells and have different HLA restrictions; and 3) the availability of a polyvalent melanoma antigen vaccine that contains these peptides. The specific goals of this project are to investigate: 1) Whether the induction of CD8+ T cells responses to defined antigens in a vaccine for melanoma can be used as a marker of the vaccine's immunological activity. 2) Whether the induction of CD8+ T cells to antigens in the vaccine is an intermediate marker of vaccine activity which is predictive of an improved clinical outcome, and the predictive value of this assay compared to other assays of vaccine immunogenicity. The study will be conducted in the context of ongoing clinical trials of a polyvalent vaccine for melanoma that contains multiple antigens recognized by CD8+ T cells. The potential clinical applications of this work include providing a method to evaluate the potency of cancer vaccines, an intermediate marker of vaccine activity which may be predictive of an improved clinical outcome, and identifying subsets of patients who are benefiting from vaccine treatment.

描述(改编自《调查员摘要》)：调查员的 目的是确定一种新的多肽特异性CD8+T细胞检测方法 对癌症疫苗的反应可以用来评估免疫学 评估疫苗的活性，并预测其临床效果。这 该提案利用了研究人员实验室的几项最新进展 与临床：1)多肽特异性CD8+T细胞检测新方法的建立 足够敏感的细胞，可以检测到疫苗诱导的增加 外周血中的这些细胞不需要体外致敏； 2)重要黑色素瘤抗原多肽组的鉴定 它们由人类CD8+T细胞识别，具有不同的人类白细胞抗原 限制；以及3)多价黑色素瘤抗原的可用性 含有这些多肽的疫苗。 该项目的具体目标是调查：1)是否 猪瘟疫苗中CD8+T细胞对特定抗原的诱导反应 黑色素瘤可以作为疫苗免疫活性的标志。 2)疫苗中CD8+T细胞对抗原的诱导是否为 疫苗活性的中间标记物，可预测改进的 临床结果，以及与其他方法相比这项检测的预测价值 疫苗免疫原性测定。该研究将在 正在进行的黑色素瘤多价疫苗临床试验的背景 含有CD8+T细胞识别的多种抗原。潜力 这项工作的临床应用包括提供一种评估方法 癌症疫苗的效力，疫苗活性的中间标志 这可能预示着临床结果的改善，并确定 受益于疫苗治疗的患者亚群。