Immunological analysis of targeted cancer therapy using light-emitting bacteria

Objectives Bacteria-mediated cancer therapy nowadays shows many promising advantages in cancer treatment compared to other conventional therapies. We have used two bioluminescent bacterial strains Salmonella typhimurium defective in synthesis of ppGpp (StΔppGpp-lux) and E.coli MG1655 (E.coli-lux) to treat ectopic CT26 colon cancer, however, their therapeutic efficacy was different. After tail vein injection of bacteria in tumor-bearing mice, initial tumor suppression was observed only with StΔppGpp-lux, but not with E.coli-lux. We hypothesized that one of the reasons of tumor regression in StΔppGpp-lux-treated group would be the strong immune-reaction between bacteria, tumor cells and immune cells inside tumor milieu, which couldn’t be elicited by systemic injection of E.coli-lux. Immunological analysis was carried out by examining the cytokine profile in tumor mass after StΔppGpp-lux and E.coli-lux infection.

Methods CT26 tumor-bearing mice were intravenously injected with StΔppGpp-lux or E.coli-lux and the tumor mass were removed at 5 dpi (‘suppression stage’) or when the tumor volume reach 1.500 mm³ (‘recurred stage’) to compare the cytokine expression in tumor mass.

Results Significant increase of mRNA and protein level of IL-1β and TNF-α was observed only in the tumor at ‘suppression stage’ of StΔppGpp-lux-treated group whereas in ‘recurred stage’, those levels returned to that before the treatment. Other cytokines such as IL-6, IL-10, IL-12, IFN-γ and TGF-β remained at basal level in both stages with either StΔppGpp-lux or E.coli-lux-infected tumors. These results indicate that IL-1β and TNF-α would play special role in the tumor suppression after StΔppGpp-lux treatment as well as provide the bases for a novel therapy.

Conclusions These results indicate the specific role of IL-1β and TNF-α in suppression tumor after StΔppGpp/lux treatment as well as provide the bases for a novel combination therapy