Fc-engineered monoclonal antibodies to reduce off-target liver uptake.

ABSTRACT:

Background

Radiolabeled-antibodies usually display non-specific liver accumulation that may impair image analysis and antibody biodistribution. Here, we investigated whether Fc silencing influenced antibody biodistribution. We compared recombinant ⁸⁹Zr-labeled antibodies (human IgG1 against different targets) with wild-type Fc and with mutated Fc (LALAPG triple mutation to prevent binding to Fc gamma receptors; FcγR). After antibody injection in mice harboring xenografts of different tumor cell lines or of immortalized human myoblasts, we analyzed antibody biodistribution by PET-CT and conventional biodistribution analysis.

Results

Accumulation in liver was strongly reduced and tumor-specific targeting was increased for the antibodies with mutated Fc compared with

SUBMITTER: Mangeat T 

PROVIDER: S-EPMC10495296 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature