Targeting CD16A on NK cells and GPC3 in hepatocellular carcinoma: development and functional validation of a therapeutic bispecific antibody.

ABSTRACT:

Introduction

Advanced hepatocellular carcinoma (HCC) poses significant therapeutic challenges due to chemotherapy resistance and limited efficacy of current targeted therapies. To address this unmet need, we developed a bispecific antibody (BsAb) platform targeting CD16A on natural killer (NK) cells and glypican-3 (GPC3), a tumor-specific antigen overexpressed in 70% of HCC cases.

Methods

High-affinity anti-CD16A single-chain variable fragments (scFvs) were selected via phage display, followed by engineering of Fc-stabilized BsAbs (MA4-hFc(N297A)-CD16A series) to minimize FcγR-mediated toxicity. Functional validation included binding kinetics (ELISA, flow cytometry, and fluorescence co-localization analysis), in vitro cytotoxicity assays (luciferase-based killing), an

SUBMITTER: Chen L 

PROVIDER: S-EPMC12198245 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature