表位
单克隆抗体
体内
体外
人源化抗体
抗体
免疫组织化学
Tau病理学
表位定位
免疫疗法
τ蛋白
病理
生物
分子生物学
阿尔茨海默病
化学
医学
免疫学
疾病
生物化学
免疫系统
遗传学
作者
Kristof Van Kolen,Thomas J. Malia,Clara Theunis,Rupesh Nanjunda,Alexey Teplyakov,Robin Ernst,Sheng-Jiun Wu,Jinquan Luo,M. Borgers,Marc Vandermeeren,Astrid Bottelbergs,Cindy Wintmolders,Eilyn R. Lacy,Hervé Maurin,Peter Stein Larsen,Roland Willems,Tom Van De Casteele,Gallen Triana-Baltzer,Randy Slemmon,Wendy R. Galpern,John Q. Trojanowski,Hong Sun,Marc Mercken
摘要
Background: As a consequence of the discovery of an extracellular component responsible for the progression of tau pathology, tau immunotherapy is being extensively explored in both preclinical and clinical studies as a disease modifying strategy for the treatment of Alzheimer’s disease. Objective: Describe the characteristics of the anti-phospho (T212/T217) tau selective antibody PT3 and its humanized variant hPT3. Methods: By performing different immunization campaigns, a large collection of antibodies has been generated and prioritized. In depth, in vitro characterization using surface plasmon resonance, phospho-epitope mapping, and X-ray crystallography experiments were performed. Further characterization involved immunohistochemical staining on mouse- and human postmortem tissue and neutralization of tau seeding by immunodepletion assays. Results and Conclusion: Various in vitro experiments demonstrated a high intrinsic affinity for PT3 and hPT3 for AD brain-derived paired helical filaments but also to non-aggregated phospho (T212/T217) tau. Further functional analyses in cellular and in vivo models of tau seeding demonstrated almost complete depletion of tau seeds in an AD brain homogenate. Ongoing trials will provide the clinical evaluation of the tau spreading hypothesis in Alzheimer’s disease.
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