Diagnostic & targeting reagents for lung cancer

诊断

• 批准号: 7495880
• 负责人: Kathlynn C Brown
• 金额: $ 4.98万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-07 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7495880
• 关键词: Affinity; Animal Model; Bacteriophages; Binding; Biochemical; Biological Assay; Biological Markers; Cancer cell line; Cancerous; Cell Surface Receptors; Cell surface; Cells; Classification; Clinical; Diagnosis; Diagnostic; Drug Delivery Systems; Future; Generations; Goals; Human; Immunohistochemistry; In Vitro; Laboratories; Libraries; Ligands; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Methodology; Methods; Mutagenesis; Normal tissue morphology; Pattern; Peptides; Phage Display; Pharmaceutical Preparations; Reagent; Specificity; Surface; Technology; Testing; Therapeutic; Tissues; Translating; United States; Woman; base; cancer cell; cancer diagnosis; carcinogenesis; cell type; in vivo; insight; men; neoplastic cell; receptor; scaffold; small molecule; targeted delivery; tumor; uptake

Lung cancer is the largest cancer killer of both men and women in the United States. Discoveryof ligands specific to receptor(s) on a surface of a lung cancer cell will impact clinical issues including functional diagnosis andcell-specific drug delivery. Our overall goal is to generate a panel of cell- specific molecules that couldbe used to classify tumor types and then be exploited for targeted delivery of therapeutics. Using phage display technologies, my laboratory has developed platform methodologies to isolate peptides that bind to and mediate uptake into specific cells. We have successfully identified cell-specific targeting peptides for 30 different cell types, including 7 cancer cell lines. The isolated peptides display remarkable cell-specificities, even among similar cells, and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. This high discriminating power suggests that peptides could be identified that selectively bind to differenttumor types, even those with similar classifications. We propose to isolate cell-targeting peptides for 16 different lung cancer lines and then utilize these peptides as diagnostic and tumor specific delivery reagents. These peptides will be assayed for affinity and cell-specificity. Efforts will be directed towards translating the targeting phage into small molecule targeting reagents and these peptide scaffoldswill be utilized to deliver therapeutics to tumor cells both in vitro and in vivo. The cell specificity demonstrated by these peptides indicates that they are recognizing distinct cell surface receptors that may be of clinical value as biomarkers for lung cancer. Thus, we will utilize the peptides to identify the cellular these unique cellular features. We will then explore the expression patterns of the receptor on a panel of human lung cancer tissues by immunohistochemistry and compare this with the expression level in matched normal tissues. Achieving our goals will impact lung cancer diagnosis and treatment as well as solving general challenges in the field of targeted drug delivery.

肺癌是美国男性和女性最大的癌症杀手。发现 肺癌细胞表面受体的特异性配体将影响临床问题，包括 功能诊断和细胞特异性药物输送。我们的总体目标是生成一组细胞- 可用于对肿瘤类型进行分类，然后用于靶向治疗的特定分子 提供治疗。我实验室利用噬菌体展示技术开发了平台 分离与特定细胞结合并介导摄取的肽的方法。我们有 成功鉴定出针对 30 种不同细胞类型（包括 7 种癌细胞）的细胞特异性靶向肽 线。分离的肽即使在相似的细胞中也表现出显着的细胞特异性，并且能够 区分正常细胞和癌细胞以及不同的肺肿瘤细胞。这个高 区分能力表明可以鉴定出选择性结合不同肿瘤的肽 类型，甚至是具有相似分类的类型。我们建议分离细胞靶向肽 16 不同的肺癌系，然后利用这些肽作为诊断和肿瘤特异性递送 试剂。将分析这些肽的亲和力和细胞特异性。努力的方向将是 将靶向噬菌体翻译成小分子靶向试剂，这些肽支架将 可用于在体外和体内向肿瘤细胞递送治疗剂。细胞特异性 这些肽表明它们正在识别不同的细胞表面受体 作为肺癌的生物标志物可能具有临床价值。因此，我们将利用肽来鉴定 细胞这些独特的细胞功能。然后我们将探索受体在 通过免疫组织化学方法对人肺癌组织进行分组，并将其与表达进行比较 匹配的正常组织中的水平。实现我们的目标将影响肺癌的诊断和治疗 以及解决靶向药物输送领域的普遍挑战。