A recycling anti-transferrin receptor-1 monoclonal antibody as an efficient therapy for erythroleukemia through target up-regulation and antibody-dependent cytotoxic effector functions.

ABSTRACT: Targeting transferrin receptor 1 (TfR1) with monoclonal antibodies is a promising therapeutic strategy in cancer as tumor cells often overexpress TfR1 and show increased iron needs. We have re-engineered six anti-human TfR1 single-chain variable fragment (scFv) antibodies into fully human scFv₂-Fcγ1 and IgG1 antibodies. We selected the more promising candidate (H7), based on its ability to inhibit TfR1-mediated iron-loaded transferrin internalization in Raji cells (B-cell lymphoma). The H7 antibody displayed nanomolar affinity for its target in both formats (scFv₂-Fcγ1 and IgG1), but cross-reacted with mouse TfR1 only in the scFv₂-Fc format. H7 reduced the intracellular labile iron pool and, contrary to what has been observed with previously described anti-

SUBMITTER: Neiveyans M 

PROVIDER: S-EPMC6512944 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature