Size-dependent effect of site-specific polyethylene glycol modification of trastuzumab on the antibody functions

Polymer modification of antibodies has attracted interest for improving their functionality. Researchers have explored modifying antibodies with polyethylene glycol (PEG) or biopolymers like antibody-oligonucleotide conjugates. While direct impacts of these modifications at the site of modification have been understood, the influence of modifications on intrinsic antibody functions, such as antigen-binding and Fc receptor-binding activities, has remained less clear.

To investigate these effects, a study prepared site-specifically PEGylated trastuzumab. The research aimed to evaluate how the modification site and the size of PEG chains impact antibody functions. The findings, revealed through reporter gene assays, showed a significant reduction in antibody-dependent cell cytotoxicity (ADCC) activity. This reduction was observed in a site- and size-dependent manner.

The study discovered that both the interaction with the antigen and Fc{gamma}RIIIa were reduced in a size-dependent manner. Interestingly, the impact of the modification site only affected ADCC activity, indicating that the higher-order structure of the modified antibody plays a crucial role in effector functions. These results provide valuable molecular design guidelines for the polymer modification of antibodies.