Tau antibody chimerization alters its charge and binding, thereby reducing its cellular uptake and efficacy.

ABSTRACT:

Background

Bringing antibodies from pre-clinical studies to human trials requires humanization, but this process may alter properties that are crucial for efficacy. Since pathological tau protein is primarily intraneuronal in Alzheimer's disease, the most efficacious antibodies should work both intra- and extracellularly. Thus, changes which impact uptake or antibody binding will affect antibody efficacy.

Methods

Initially, we examined four tau mouse monoclonal antibodies with naturally differing charges. We quantified their neuronal uptake, and efficacy in preventing toxicity and pathological seeding induced by human-derived pathological tau. Later, we generated a human chimeric 4E6 (h4E6), an antibody with well documented efficacy in multiple tauopathy models. We compared

SUBMITTER: Congdon EE 

PROVIDER: S-EPMC6492224 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature