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.
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Hoffman, R.M., Zhao, M. (2016). Methods for Tumor Targeting with Salmonella typhimurium A1-R. In: Hoffman, R. (eds) Bacterial Therapy of Cancer. Methods in Molecular Biology, vol 1409. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3515-4_13
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DOI: https://doi.org/10.1007/978-1-4939-3515-4_13
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