title: Methods for Tumor Targeting with Salmonella typhimurium A1-R.
abstract: Salmonella typhimurium A1-R (S. typhimurium A1-R) has shown great preclinical promise as a broad-based anti-cancer therapeutic (please see Chapter 1 ). The present chapter describes materials and methods for the preclinical study of S. typhimurium A1-R in clinically-relevant mouse models. Establishment of orthotopic metastatic mouse models of the major cancer types is described, as well as other useful models, for efficacy studies of S. typhimurium A1-R or other tumor-targeting bacteria, as well. Imaging methods are described to visualize GFP-labeled S. typhimurium A1-R, as well as GFP- and/or RFP-labeled cancer cells in vitro and in vivo, which S. typhimurium A1-R targets. The mouse models include metastasis to major organs that are life-threatening to cancer patients including the liver, lung, bone, and brain and how to target these metastases with S. typhimurium A1-R. Various routes of administration of S. typhimurium A1-R are described with the advantages and disadvantages of each. Basic experiments to determine toxic effects of S. typhimurium A1-R are also described. Also described are methodologies for combining S. typhimurium A1-R and chemotherapy. The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies.
authors: AntiCancer Inc. and Department of Surgery, University of California - San Diego, San Diego, CA, USA. all@anticancer.com.
authors: Robert M
authors: RM
authors: Hoffman
authors: AntiCancer Inc., San Diego, CA, USA.
authors: Ming
authors: M
authors: Zhao
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D005818:Genetic Engineering; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D012486:Salmonella typhimurium / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007371:Interferon-gamma
keywords: Amino acid; Auxotroph; Cancer; Green fluorescent protein (GFP); Leu-Arg; Metastasis; Mouse models; Nude mice; Orthotopic; Salmonella typhimurium A1-R; Surgical orthotopic implantation (SOI); Tumor targeting