CAREER: The Role of Mobility in Antibody Aggregation

教师早期职业发展项目的研究目标是预测单克隆型抗体的聚集动力学，并探索延长抗体货架期的新策略。抗体在疾病治疗和医学诊断中具有重要意义。聚集性是抗体药物制造、输送和储存过程中的一个重要问题。因为一旦聚集，展开的抗体将无法识别或结合抗原，这将降低药物疗效，并可能引起有害的免疫反应。为了实现这一目标，建议的研究方法是：(A)确定单抗在药物溶液中的迁移率的作用，(B)预测聚集动力学，以及(C)提供促进抗体药物开发的计算工具。模型将针对光散射、光谱学和流变学实验进行开发和验证。获得高质量、浓缩但低成本的抗体药物具有巨大的经济和社会影响。如果成功，该项目将加强抗体的制造和储存过程，这可以节省数十亿美元的医疗成本，并使挽救生命的药物广泛获得，特别是在发展中国家。这个综合研究和教育项目将为工程和制药科学专业的学生提供纳米生物力学的跨学科培训。将开发创新的建模课程。这些科学材料将向高中教师和K-12学生演示，并将通过播客技术向公众提供。先进成果还将在科学研讨会上传播。

The research objective of this Faculty Early Career Development (CAREER) project is to predict the aggregation kinetics of monoclonal-type antibodies, and to explore novel strategies to prolong antibody's shelf life. Antibody is important for disease treatment and medical diagnosis. Aggregation is a critical concern in antibody drug manufacturing, delivery, and storage. Because once aggregated, the unfolded antibodies will fail to recognize or bind antigens, which will reduce the drug efficacy and may cause harmful immune responses. To achieve the goal, the proposed research approaches are to: (a) identify the role of mobility of monoclonal antibodies in drug solutions, (b) predict the aggregation kinetics, and (c) provide a computational tool that can facilitate the antibody drug development. Models will be developed and validated against light scattering, spectroscopy, and rheological experiments.Availability of high quality, concentrated, yet low cost antibody drug has great economical and societal impacts. If successful, the project will enhance the antibody manufacturing and storage processes, which can save billions in healthcare costs and make the life-saving medicines broadly available especially in developing countries. The integrated research and education project will provide interdisciplinary training on nano-bio-mechanics for students in engineering and pharmaceutical science programs. Innovated modeling courses will be developed. The scientific materials will be demonstrated to high school teachers and K-12 students and will be made available to public using podcasting technology. Advanced results will also be disseminated in a scientific workshop.