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VNP20009-CCL2-CXCL9 is an investigational bacteria-mediated cancer therapy being developed for osteosarcoma with pulmonary metastasis. It is a novel, genetically engineered strain of *Salmonella typhimurium* (VNP20009) that is designed to express the chemokines CCL2 and CXCL9. Leveraging the natural tendency of the VNP20009 bacterial strain to accumulate in tumors, the therapy aims to deliver these chemokines directly to the tumor microenvironment (TME). Once in the tumor, VNP20009-CCL2-CXCL9 triggers immunogenic cell death and activates the cGAS/STING pathway, promoting a type I interferon response. The locally produced CCL2 and CXCL9 then recruit key immune cells, including dendritic cells (DCs), macrophages (Mφs), and T cells, into the TME. This process is intended to convert an immunosuppressive TME into a pro-inflammatory one, reprogramming macrophages to an anti-tumor phenotype, inducing DC maturation, and significantly increasing T-cell infiltration and activation, ultimately leading to innate and adaptive anti-tumor immune responses. Research in mouse models has shown that this approach can inhibit the progression of osteosarcoma lung metastasis and improve survival.
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