Macrophage-Engaging IgG4 Antibody Triggers Cytotoxicity Against Integrin αvβ3+ Cancers.

ABSTRACT: Integrin αvβ3, absent in most normal cells, has emerged as both a marker and a driver of tumor stemness and drug resistance in epithelial cancers, making it an attractive therapeutic target. The humanized IgG1 anti-αvβ3 antibody, etaracizumab, was originally developed to exploit NK cell-mediated cytotoxicity against αvβ3-positive tumors. However, despite its favorable safety profile and clinical efficacy, its impact was insufficient for further development. We previously discovered that αvβ3-positive epithelial tumors exhibit a tumor-associated macrophage (TAM)-rich microenvironment with limited NK cell infiltration, potentially limiting the effectiveness of etaracizumab. Here, we hypothesized that re-engineering the anti-αvβ3 antibody to activate TAM-mediated cytotoxicity would enhance it

SUBMITTER: Reddy JP 

PROVIDER: S-EPMC12570272 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature