Abstract
Triple-negative breast cancer (TNBC) is a refractory tumor type with high morbidity and poor outcome in clinic, novel approaches are required to improve the clinical benefits for patients. T-cell redirecting bispecific antibodies represent an emerging technology for cancer immunotherapy, which could directly engage T-cells with tumor antigens without MHC restriction. In this study, bispecific anti-EphA2/CD3 antibodies and the co-stimulatory molecules CD80/86 expressed on the surface of M1 macrophages, which deliver the first and second signals required for T cell activation, were co-expressed on mixed vesicle membranes. Additionally, the cytokine IL-12 was encapsulated within the vesicles, constructing bispecific antibody armed hybrid membrane nano-vesicles (M1-BANV@IL-12) for the treatment of TNBC. The results demonstrated that M1-BANV@IL-12 could efficiently recruit and activate T cells, effectively inhibiting TNBC. This study proposed a novel vesicular antibody strategy that effectively activates T cells, providing a promising therapeutic approach for improved TNBC immunotherapy.

文章链接:https://doi.org/10.1016/j.cej.2025.171773