Long lasting complement neutralisation by RAY121, an engineered anti-C1s antibody with C1q displacement function.

ABSTRACT:

Background

Antibody drugs blocking the complement classical pathway (CP) often require frequent intravenous administration to overcome the high abundance or rapid turnover of complement proteins. This makes treatment compliance burdensome for patients.

Methods

Screening was performed to identify anti-C1s antibodies specific for the CUB domain of C1s with CP neutralising function. Antibody engineering was performed on the anti-C1s antibody to prolong its half-life in circulation. The variable region was mutated to confer pH-dependent binding to C1s, and the antibody Fc was modified to lower its isoelectric point and to have enhanced binding to the neonatal Fc receptor.

Findings

A combination of pH-dependent binding to C1s and optimisation of charge characteristics was

SUBMITTER: Ho AWS 

PROVIDER: S-EPMC12639577 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature