title: Cancer metastasis directly eradicated by targeted therapy with a modified Salmonella typhimurium.
abstract: Cancer metastasis is the life-threatening aspect of cancer and is usually resistant to standard treatment. We report here a targeted therapy strategy for cancer metastasis using a genetically-modified strain of Salmonella typhimurium. The genetically-modified strain of S. typhimurium is auxotrophic for the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in cancer cells. The tumor-targeting strain of S. typhimurium, termed A1-R, and expressing green fluorescent protein (GFP), was administered to both axillary lymph and popliteal lymph node metastasis of human pancreatic cancer and fibrosarcoma, respectively, as well as lung metastasis of the fibrosarcoma in nude mice. The bacteria were delivered via a lymphatic channel to target the lymph node metastases and systemically via the tail vein to target the lung metastasis. The cancer cells expressed red fluorescent protein (RFP) in the cytoplasm and GFP in the nucleus linked to histone H2B, enabling color-coded real-time imaging of the bacteria targeting the metastatic tumors. After 7-21 days of treatment, the metastases were eradicated without the need of chemotherapy or any other treatment. No adverse effects were observed. This new strategy demonstrates the clinical potential of targeting and curing cancer metastasis with engineered bacteria without the need of toxic chemotherapy.
authors.affiliation: AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Kensuke
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tomita
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins