Enhancement of therapeutic potential of a naturally occurring human antibody targeting a phosphorylated Ser⁴²² containing epitope on pathological tau.

ABSTRACT: Aggregation of tau protein and spreading of tau aggregates are pivotal pathological processes in a range of neurological disorders. Accumulating evidence suggests that immunotherapy targeting tau may be a viable therapeutic strategy. We have previously described the isolation of antibody CBTAU-22.1 from the memory B-cell repertoire of healthy human donors. CBTAU-22.1 was shown to specifically bind a disease-associated phosphorylated epitope in the C-terminus of tau (Ser⁴²²) and to be able to inhibit the spreading of pathological tau aggregates from P301S spinal cord lysates in vitro, albeit with limited potency. Using a combination of rational design and random mutagenesis we have derived a variant antibody with improved affinity while maintaining the specificity of the parental

SUBMITTER: van Ameijde J 

PROVIDER: S-EPMC6042391 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature