This study investigates a novel bacterial-mediated tumor therapy using an engineered strain of Salmonella typhimurium. The bacteria selectively target solid tumors, delivering a therapeutic fusion peptide that induces necrotic cell death and tumor reduction.
Begin with mice bearing solid tumors implanted subcutaneously in the thigh.
Inject the mice via the tail vein with a non-virulent, engineered strain of Salmonella typhimurium.
The bacteria circulate in the bloodstream and selectively accumulate in the hypoxic, immunosuppressed tumor microenvironment.
They carry a plasmid encoding a therapeutic fusion peptide composed of a cell-penetrating peptide and the mitochondrial target domain of a pro-apoptotic protein, along with phage-derived lysis proteins.
These genes are regulated by L-arabinose-inducible promoters.
Administer L-arabinose intraperitoneally to induce bacterial gene expression and protein production.
The lysis proteins trigger bacterial rupture, releasing the fusion peptide into the tumor microenvironment.
The CPP penetrates the tumor cell membrane, enabling MTD entry.
Once inside the cell, the MTD disrupts mitochondrial membranes, inducing calcium release and resulting in cytoplasmic calcium overload, necrotic cell death, and subsequent tumor reduction.
This demonstrates the efficacy of bacteria-mediated tumor therapy.
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