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Updated: Apr 5, 2026
Measuring Growth and Gene Expression Dynamics of Tumor-Targeted S. Typhimurium Bacteria
Published on: July 6, 2013
Genetically modified "obligate" anaerobic Salmonella typhimurium as a therapeutic strategy for neuroblastoma
Zhu-Ling Guo1, Bin Yu2,3, Bo-Tao Ning4
1Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, SAR, People's Republic of China. guochenyan07@gmail.com.
Background:
Neuroblastoma currently has poor prognosis, therefore we proposed a new strategy by targeting neuroblastoma with genetically engineered anaerobic Salmonella (Sal-YB1).
Methods:
Nude and nonobese diabetic-severe combined immunodeficiency (NOD-SCID) orthotopic mouse models were used, and Sal-YB1 was administered via tail vein. The therapeutic effectiveness, bio-safety, and mechanisms were studied.
Results:
No mice died of therapy-related complications. Tumor size reduction was 70 and 30% in nude and NOD-SCID mice, respectively. No Salmonella was detected in the urine; 75% mice had positive stool culture if diaminopimelic acid was added, but all turned negative subsequently. Tumor tissues had more Sal-YB1 infiltration, necrosis, and shrinkage in Sal-YB1-treated mice. Significantly higher expression of TLR4, TNF-stimulated gene 6 protein (TSG6), and cleaved caspase 1, 3, 8, and 9 was found in the tumor masses of the Sal-YB1-treated group with a decrease of interleukin 1 receptor-associated kinase (IRAK) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα). There was a high release of TNFα both in human macrophages and mouse tumor tissues with Sal-YB1 treatment. The antitumor effect of the supernatant derived from macrophages treated with Sal-YB1 could be reversed with TNFα and pan-caspase inhibitors.
Conclusions:
This new approach in targeting neuroblastoma by bio-engineered Salmonella with the assistance of macrophages indirectly may have a clinical therapeutic impact in the future.
