Abstract
One of the primary limitations of cancer gene therapy is lack of selectivity of the therapeutic gene to tumor cells. Current efforts are focused on discovering and developing tumor-targeting vectors that selectively target only cancer cells but spare normal cells to improve the therapeutic index. The use of preferentially tumor-targeting bacteria as vectors is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative-anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. In this study, we exploited attenuated Salmonella as a tumoricidal agent and a vector to deliver genes for tumor-targeted gene therapy. Attenuated Salmonella, carrying a eukaryotic expression plasmid encoding an anti-angiogenic gene, was used to evaluate its’ ability for tumor targeting and gene delivery in murine tumor models. We also investigated the use of a polymer to modify or shield Salmonella from the pre-existing immune response in the host in order to improve gene delivery to the tumor. These results suggest that tumor-targeted gene therapy using Salmonella carrying a therapeutic gene, which exerts tumoricidal and anti-angiogenic activities, represents a promising strategy for the treatment of tumors.
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References
Pawelek JM, Low KB, Bermudes D (2003) Bacteria as tumour-targeting vectors. Lancet Oncol 4:548–556
Pawelek JM, Low KB, Bermudes D (1997) Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res 57:4537–4544
Zhao M, Yang M, Li XM, Jiang P, Baranov E, Li S, Xu M, Penman S, Hoffman RM (2005) Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proc Natl Acad Sci U S A 102:755–760
Lee CH, Wu CL, Shiau AL (2004) Endostatin gene therapy delivered by Salmonella choleraesuis in murine tumor models. J Gene Med 6:1382–1393
Dang LH, Bettegowda C, Huso DL, Kinzler KW, Vogelstein B (2001) Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci U S A 98:15155–15160
Yazawa K, Fujimori M, Amano J, Kano Y, Taniguchi S (2000) Bifidobacterium longum as a delivery system for cancer gene therapy: selective localization and growth in hypoxic tumors. Cancer Gene Ther 7:269–274
Lee CH, Wu CL, Tai YS, Shiau AL (2005) Systemic administration of attenuated Salmonella choleraesuis in combination with cisplatin for cancer therapy. Mol Ther 11:707–716
Lee CH, Hsieh JL, Wu CL, Hsu PY, Shiau AL (2011) T cell augments the antitumor activity of tumor-targeting Salmonella. Appl Microbiol Biotechnol 90:1381–1388
Liu F, Zhang L, Hoffman RM, Zhao M (2010) Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity. Cell Cycle 9:4518–4524
Nagakura C, Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Bouvet M, Hoffman RM (2009) Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice. Anticancer Res 29:1873–1878
Lee CH, Wu CL, Shiau AL (2005) Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model. Cancer Gene Ther 12:175–182
Ganai S, Arenas RB, Forbes NS (2009) Tumour-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival in mice. Br J Cancer 101:1683–1691
Lee CH, Wu CL, Chen SH, Shiau AL (2009) Humoral immune responses inhibit the antitumor activities mediated by Salmonella enterica serovar Choleraesuis. J Immunother 32:376–388
Lee CH, Lin YH, Hsieh JL, Chen MC, Kuo WL (2013) A polymer coating applied to Salmonella prevents the binding of Salmonella-specific antibodies. Int J Cancer 132:717–725
Lee CH (2012) Engineering bacteria toward tumor targeting for cancer treatment: current state and perspectives. Appl Microbiol Biotechnol 93:517–523
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Lee, CH. (2016). Employment of Salmonella in Cancer Gene Therapy. 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_8
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DOI: https://doi.org/10.1007/978-1-4939-3515-4_8
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