GFRAL-Fc disarms GDF15 to reprogram tumor immunity and amplify PD-1 efficacy in hepatocellular carcinoma.

ABSTRACT:

Background

Checkpoint inhibitors have revolutionized hepatocellular carcinoma (HCC) treatment, yet their efficacy remains limited in advanced stages, with suboptimal objective response rates. Growth differentiation factor 15 (GDF15), a dual-functional cytokine implicated in tumor progression and immunosuppression, represents a promising therapeutic target. This study aims to develop a novel GDF15-targeted strategy to improve HCC management and synergize with PD-1 blockade.

Methods

GFRAL-Fc fusion proteins were generated by fusing the extracellular domain of GFRAL with IgG1 Fc. The anti-tumor efficacy and the anti-cachexia ability of GFRAL-Fc was evaluated in a spontaneous HCC model on GDF15 humanized mice. Additionally, the half-life and drug safety were evaluated in mice. T

SUBMITTER: Shi G 

PROVIDER: S-EPMC12522818 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature