Comparison Of Anticancer Activity And Biosafety With Different Engineered Attenuated Bacteria

Salmonella typhimurium strains ΔppGpp is an attenuated strain with good biosafety and excellent anticancer efficacy.The deletion of rel A and spo T genes makes it deficient in guanosine-5’-bisphosphate-3’-bisphosphate-synthesis(ppGpp).The strain has been applied in preclinical studies of anticancer therapy for various kinds of solid cancers.VNP20009 is another genetically modified nutritionally deficient strain with deletion of pur I and msb B,which has shown good therapeutic efficacy in various preclinical tumor models and entered phase I clinical trials.Here,the invasion activities and virulence of ΔppGpp was found to be significantly lower than those of VNP20009 strain when tested with cancer cells in vitro.In addition,the MC38tumor-bearing mice showed equally suppressed cancer growth in average when treated with ΔppGpp or VNP20009 intravenously.However,the ΔppGpp-treated mice showed16.7% of complete cancer eradication and elongated survival in mice,whereas VNP20009 showed worsened cytotoxicity to animals,even with quite equal tumor size in individual mice.Inflammatory cytokine analysis also showed a decreased level in circulation but strengthened immune boost in tumor microenvironments.In this study,the antitumor activity and biosafety of ΔppGpp and VNP20009 strains were compared in vivo and in vitro,which is expected to promote the clinical transformation ofΔppGpp strain to provide some experimental basis.Taken together,the engineeredΔppGpp might have greater potential for cancer therapeutics than VNP20009,and should be a promising approach in clinical translation of cancer therapy.