Turning aging cells into a live vaccine: engineered senescent cancer cells with adjuvant celecoxib for immunotherapy

The immunoactivation effects of senescent tumor cells are a potential avenue for cancer therapy. They can act as antigen reservoirs for cancer vaccination, but how to maintain strong immunogenicity to induce a robust immunity is underexplored. In this study, we developed an engineered live vaccine composed of hydrogel-encapsulated senescent tumor cells and liposomal celecoxib (STCs+CLX-Lipo@Gel). This vaccine prolongs the in vivo persistence of senescent tumor cells and utilizes liposomal celecoxib (COX2 inhibitor) to promote the recruitment and maturation of dendritic cells (DC). Notably, a single dose can significantly delay melanoma growth by eliciting robust immunity. The vaccine extended the survival of mice with melanoma brain metastases. Moreover, this strategy also demonstrated high efficacy against orthotopic pancreatic tumors. This study presents a comprehensive strategy to boost the immunogenicity of whole-tumor-cell vaccines by leveraging senescent tumor cells and COX2 inhibition, with treatment efficacy in various tumor models. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/694320v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@f08fforg.highwire.dtl.DTLVardef@117d0aborg.highwire.dtl.DTLVardef@849665org.highwire.dtl.DTLVardef@adcf83_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphic summary.C_FLOATNO Schematic illustration of the preparation of live-cell vaccines and the tumor-specific immune responses elicited by the vaccine. Created with BioRender.com. C_FIG