CD11b agonist GB1275 potentiates oncolytic bacterial therapy against pancreatic cancer in mouse tumor models
2026-08-21
Oncolytic bacteria are microorganisms with cytotoxic activity capable of lysing cancer cells while simultaneously activating both innate and adaptive immune responses to exert anti-tumor effects. However, the innate immune activation targeting oncolytic bacteria within the tumor microenvironment (TME) is a limiting factor. Here we find that the CD11b-targeting agonist GB1275 can modulate bacteria-immune interaction and inhibit the infiltration of CD11b⁺ innate immune cells such as neutrophils and macrophages, thereby suppressing the antimicrobial immune defenses in the TME in mice. This then avoids the clearance of oncolytic bacteria and increases the efficacy of bacteria-mediated tumor immunotherapy. Furthermore, the gemcitabine-loaded bacteria combined with GB1275 treatment activate innate immune responses in tumor, as mediated by Toll-like receptors (TLR), NOD-like receptors (NLR) and cGAS-STING pathways, while simultaneously enhancing dendritic cell (DC)-dependent antigen cross-presentation; this then upregulates the adaptive anti-tumor immune response and inhibits the growth of both subcutaneous and in situ pancreatic cancers in mouse tumor models. Our results therefore demonstrate that modulating innate immune responses while subsequently strengthening adaptive immune activation can significantly improve the efficacy of bacteria-mediated tumor immunotherapy.