DETECTION OF METASTASIS ASSOCIATED ANTIGENS IN MELANOMA

黑色素瘤中转移相关抗原的检测

• 批准号: 2724710
• 负责人: CARL Venton HAMBY
• 金额: $ 11.75万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-06 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2724710
• 关键词: antibody; biomarker; circulating neoplastic cell; early diagnosis; melanoma; metastasis; tissue /cell culture

DESCRIPTION: (adapted from the investigator's abstract) The major cause of mortality in patients with malignant melanoma is metastatic dissemination of primary tumors. Currently, there are no highly specific cellular markers for evaluating the metastatic potential of primary melanoma tumors. The long-term goals of this project are to discover diagnostic markers for the early detection of metastatic disease in patients with melanoma and to evaluate these markers as prognostic indicators for the clinical course of disease. To identify these molecules we proposed to use a phage display library of human single-chain variable fragment (scFv) antibodies. The library contains >108 different scFv antibody specificities, which they expect is sufficiently diverse to contain scFv antibodies recognizing metastasis-associated antigens. They will utilize a panning procedure to select a subset of scFv antibodies that bind to a line of cultured human melanoma tumor cells, which are highly metastatic in nude mice. From this subset they will remove scFv antibodies that can bind to an autologous subline of weakly metastatic human melanoma tumor cells. The scFv that remain will be screened for reactivity against tissue samples of primary tumor and metastatic lesions obtained from melanoma patients. They expect to discover scFv antibodies that specifically recognize metastasis-associated antigens in human melanoma lesions. These scFv antibodies will be used for the development of early diagnostic markers and prognostic indicators of metastatic dissemination of human melanoma.

描述：(改编自调查人员的摘要)主要原因 恶性黑色素瘤患者的死亡率为转移性 原发肿瘤的扩散。目前，还没有高度具体的 评估原发肿瘤转移潜能的细胞标志物 黑色素瘤。这个项目的长期目标是发现 早期发现转移性疾病的诊断标志物 黑色素瘤患者并评估这些标志物对预后的影响 临床病程指标。 为了鉴定这些分子，我们建议使用噬菌体展示文库 人源单链可变区(ScFv)抗体。图书馆 包含&gt；108不同的单链抗体特异性，这是他们所期望的 足够多样化，足以包含识别单链抗体的单链抗体 肿瘤转移相关抗原。 他们将利用平移过程来选择scFv的子集 与培养的人类黑色素瘤肿瘤细胞系结合的抗体， 它们在裸鼠体内的转移率很高。从这个子集中，他们将 去除可与弱的自体亚系结合的单链抗体 转移性人类黑色素瘤肿瘤细胞。剩下的scFv将是 对原发肿瘤组织样本进行反应性筛查 来自黑色素瘤患者的转移性病变。 他们希望发现scFv抗体能够特异性地识别 人类黑色素瘤皮损中的转移相关抗原。这些scFv 抗体将用于开发早期诊断标记物 以及人类黑色素瘤转移性扩散的预后指标。