Engineered Salmonella enterica serovar Typhimurium overcomes limitations of anti-bacterial immunity in bacteria-mediated tumor therapy

Oncoimmunology
Sebastian FelgnerSiegfried Weiss

Abstract

Cancer is one of the leading causes of death in the industrialized world and represents a tremendous social and economic burden. As conventional therapies fail to provide a sustainable cure for most cancer patients, the emerging unique immune therapeutic approach of bacteria-mediated tumor therapy (BMTT) is marching towards a feasible solution. Although promising results have been obtained with BMTT using various preclinical tumor models, for advancement a major concern is immunity against the bacterial vector itself. Pre-exposure to the therapeutic agent under field conditions is a reasonable expectation and may limit the therapeutic efficacy of BMTT. In the present study, we investigated the therapeutic potential of Salmonella and E. coli vector strains in naïve and immunized tumor bearing mice. Pre-exposure to the therapeutic agent caused a significant aberrant phenotype of the microenvironment of colonized tumors and limited the in vivo efficacy of established BMTT vector strains Salmonella SL7207 and E. coli Symbioflor-2. Using targeted genetic engineering, we generated the optimized auxotrophic Salmonella vector strain SF200 (ΔlpxR9 ΔpagL7 ΔpagP8 ΔaroA ΔydiV ΔfliF) harboring modifications in Lipid A and flagella synthesis...Continue Reading

References

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Citations

Feb 1, 2018·BioTechniques·Hannah Martin Lawrenz
Apr 6, 2019·Cancer Medicine·Mansour SedighiEbrahim Kouhsari
May 1, 2019·Journal of Applied Microbiology·K JazeelaV K Deekshit
Dec 13, 2019·Experimental & Molecular Medicine·Mai Thi-Quynh DuongJung-Joon Min
Nov 23, 2019·International Journal of Cancer. Journal International Du Cancer·Sebastian FelgnerMarc Erhardt
Nov 19, 2018·Applied Microbiology and Biotechnology·Tingtao ChenHongbo Xin
May 17, 2018·Frontiers in Oncology·Suneesh KaimalaBasel K Al-Ramadi
Jul 23, 2020·Applied Microbiology and Biotechnology·Noura S DosokySean S Davies
Apr 16, 2021·Advanced Science·Xuehui HuangShaobing Zhou
Jul 3, 2021·Cancers·Besan H Al-SaafeenBasel K Al-Ramadi
Jul 21, 2021·BMC Microbiology·Sara EbrahimzadehShirin Eyvazi

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Methods Mentioned

BETA
genetic modifications
light microscopy
scanning electron microscopy
ELISA

Software Mentioned

BMTT
Bio
Adobe Photoshop
Plex Manager

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