Carbohydrate Microarray Profiling of Glycan-Binding Antibodies and Lectins

聚糖结合抗体和凝集素的碳水化合物微阵列分析

• 批准号: 10702399
• 负责人: Jeffrey Gildersleeve
• 金额: $ 110.5万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702399
• 关键词: Agonist; Antibodies; Basic Science; Binding; Carbohydrates; Child; Clinical; Databases; Diagnostic; Disease; Disease Progression; Engineering; Evaluation; FDA approved; Goals; Lectin; Malignant Neoplasms; Mammals; Microarray Analysis; Monoclonal Antibodies; Neuroblastoma; Play; Polysaccharides; Protein-Carbohydrate Interaction; Proteins; Reagent; Research; Role; Therapeutic Agents; antagonist; cancer cell; carbohydrate binding protein; carbohydrate database; design; high throughput technology; interest; tool; tumor; tumor progression

Carbohydrate-binding antibodies are used extensively for basic research and are useful as diagnostic and therapeutic agents. They are especially useful in the field of cancer. Cancer cells undergo dramatic changes in carbohydrate expression during the onset and progression of disease. As a result, there has been considerable interest in understanding why these changes occur, how they contribute to the disease, and exploiting these changes for clinical use. For example, Unituxin (dinituximab) is an FDA approved monoclonal antibody that targets the tumor associated carbohydrate GD2 and is used to treat children with neuroblastoma. Unfortunately, there are very few good monoclonal antibodies to carbohydrates. The lack of high quality antibodies is a major barrier for the field. We are taking a multi-pronged approach to help alleviate this problem. First, we use our glycan microarray to evaluate the selectivities of existing antibodies to carbohydrates. This information is crucial for selecting the right antibody for a particular application and interpreting results. Second, we have developed a database of antibodies to carbohydrates (Database of Anti-Glycan Reagents; DAGR) that can be used to find antibodies and information about those antibodies. Third, we are studying the mechanisms by which antibodies to carbohydrates are produced in mammals. Fourth, we are using our glycan microarray to discover and engineer new antibodies to carbohydrates

碳水化合物结合抗体被广泛用于基础研究，可用作诊断和治疗剂。它们在癌症领域特别有用。 癌细胞在发作和疾病进展过程中碳水化合物表达的急剧变化。结果，人们对理解为什么发生这些变化，如何对疾病做出贡献并利用这些变化供临床使用引起了人们的兴趣。例如，元曲（Dinituximab）是FDA认可的单克隆抗体，该抗体靶向肿瘤相关的碳水化合物GD2，用于治疗神经母细胞瘤的儿童。不幸的是，碳水化合物的良好单克隆抗体很少。 缺乏高质量抗体是该领域的主要障碍。我们正在采用多管齐下的方法来帮助缓解这一问题。首先，我们使用聚糖微阵列评估现有抗体的碳水化合物的选择性。此信息对于选择适合特定应用程序的合适抗体和解释结果至关重要。其次，我们开发了一种抗碳水化合物的抗体数据库（抗糖试剂数据库； DAGR），该数据库可用于查找有关这些抗体的抗体和信息。第三，我们正在研究哺乳动物中对碳水化合物抗体的机制。第四，我们正在使用聚糖微阵列来发现和设计新抗体的碳水化合物