Demonstrates a novel strategy to reprogram the tumor microenvironment, enhancing immunotherapy effectiveness in pediatric cancers, indicating significant clinical potential.
Key Points
The research aims to reprogram the tumor microenvironment in pediatric solid cancers to enhance T cell-mediated immunotherapies.
Screened multi-omics data to identify targets in pediatric cancers with 'cold' TME.
Developed a fusion protein targeting B7-H3, incorporating IL2 and IL12 receptor agonist domains.
Evaluated the fusion protein's efficacy in vitro for NK cell activation and macrophage polarization.
Utilized orthotopic xenograft and syngeneic mouse models to assess tumor response to therapy.
The fusion protein resulted in complete tumor eradication in the xenograft model when combined with CAR-T therapy.
It induced M2-to-M1 macrophage conversion and significant T cell infiltration in the tumor microenvironment.
Single-agent therapy with the fusion protein maintained limited toxicities while achieving sustained tumor clearance in immunocompetent mice.