Fibrin gel-based co-delivery of self-adjuvant tumor vaccine and PD-1 blockade for post-surgical gastric cancer immunotherapy.

Preventing post-surgical recurrence and metastasis in advanced gastric cancer through tumor vaccines necessitates a more surgically compatible strategy. Here, we propose an intraoperatively applicable platform featuring a self-adjuvant tumor vaccine co-delivered with PD-1 blockade in fibrin gel (FG) to inhibit post-surgical tumor relapse. First, the tumor cell membrane vaccine is modified via simple insertion of DSPE-PEG-αCD40, which simultaneously endows the vaccine with targeting and self-adjuvant effects on antigen-presenting cells (APCs). This αCD40-modified vaccine (Vax-αCD40) significantly stimulates dendritic cell maturation and reprograms macrophages toward pro-inflammatory phenotypes in vitro and in vivo. Moreover, when Vax-αCD40 and αPD-1 are encapsulated within FG to form an adhesive "vaccine pool", a positive feedback loop of CD40 expression-αCD40 stimulation on APCs exerts synergistic immune activation at the surgical site. In mouse models, this co-delivery system effectively suppresses local recurrence and peritoneal metastasis, which is associated with increased APC infiltration, cytotoxic CD8+ T cell expansion, and durable immune memory. This strategy represents a translatable approach for preventing recurrence in gastrointestinal malignancies.