Enhanced LSPR sensitivity for OpenSPR detection of therapeutic antibodies and polymer antibody conjugates

增强了 OpenSPR 检测治疗性抗体和聚合物抗体缀合物的 LSPR 灵敏度

• 批准号: 532019-2018
• 负责人: Wylie, Ryan
• 金额: $ 1.82万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=669018
• 关键词: Enhanced; LSPR; sensitivity; OpenSPR; detection

Therapeutic antibodies represent a growing class of drug that are particularly important for cancer immunotherapies. Due to biological transport barriers, many treatments fail due to the lack of antibodies reaching the disease site. Furthermore, large doses of antibodies are commonly administered, which may lead to toxic side effects. Therefore, we are developing an injectable local release system to increase antibody concentrations at the disease site, while decreasing side effects and cost. To accomplish these goals, we need methods to rapidly detect and assess the activity of therapeutic antibodies released from our delivery systems. Nicoya Lifesciences has developed the first commercial instrument, OpenSPR, based on localized surface plasmon resonance (LSPR) biosensing. Compared to other techniques, OpenSPR has a high signal to noise ratios that is amenable to cost effective high throughput analysis. Currently, OpenSPR lacks the sensitivity to detect pico to femtomole amounts of antibodies, which is required for biologically relevant release studies. To this end, we will develop procedures and materials to enhance the LSPR detection of antibodies in the OpenSPR instrument. Because LSPR measures shifts in light absorption due to refractive index changes upon antibody binding to the gold OpenSPR surface, LSPR enhancement will be accomplished by: (1) modifying antibodies with chromophores that absorb visible light; and (2) adding antibody binding peptides modified with chromophores that absorb visible light. The combination of Nicoya's LSPR technology and the Wylie lab's expertise in therapeutic antibodies will result in the development of new LSPR protocols and materials to rapidly analyze dilute antibody solutions.****

治疗性抗体代表着越来越多的药物，这些药物对癌症免疫疗法特别重要。由于生物运输障碍，许多治疗因缺乏到达病区的抗体而失败。此外，大剂量的抗体通常被注射，这可能会导致毒副作用。因此，我们正在开发一种可注射的局部释放系统，以增加疾病部位的抗体浓度，同时减少副作用和成本。为了实现这些目标，我们需要快速检测和评估从我们的递送系统释放的治疗性抗体的活性的方法。Nicoya生命科学公司开发了第一台基于局部表面等离子体共振(LSPR)生物传感的商用仪器OpenSPR。与其他技术相比，OpenSPR具有高信噪比，易于进行成本效益高的高通量分析。目前，OpenSPR缺乏检测微微克到毫微克分子抗体的灵敏度，这是生物学相关释放研究所必需的。为此，我们将制定程序和材料，以加强OpenSPR仪器中抗体的LSPR检测。由于LSPR测量由于抗体结合到金OpenSPR表面时折射率的变化而引起的光吸收的变化，LSPR增强将通过以下方式实现：(1)用吸收可见光的发色团修饰抗体；(2)添加用吸收可见光的发色团修饰的抗体结合肽。Nicoya的LSPR技术与怀利实验室在治疗性抗体方面的专业知识的结合将导致开发新的LSPR协议和材料，以快速分析稀释抗体溶液。*