Cancer Gene Therapy pp 57-63 | Cite as
Tumor-Targeted Salmonella
Highly Selective Delivery Vectors
Chapter
Summary
Genetically engineered Salmonella offer an intriguing new approach to selectively target solid tumors, including melanoma, lung, colon, breast, kidney and liver. These bacteria target tumors after systemic administration and selectively replicate within them. Specificity for tumors is often more than 1,000 times greater than for any other tissue. Auxotrophic mutations make these bacteria highly safe and form the basis for maintaining tumor specificity. An altered lipid greatly reduces the potential for septic shock yet also retains the antitumor properties of these bacteria. These bacteria have innate antitumor activity towards both primary and metastatic tumors and the ability to deliver proteins capable of activating chemotherapeutic agents directly within tumors. The delay in tumor growth results in mice that survive up to twice as long. These bacteria are susceptible to a wide range of antibiotics, allowing external control of the vector after administration. The combination of these features within a single vector seems especially surprising considering their unlikely source.
Keywords
Thymidine Kinase Cancer Gene Therapy Inhibit Tumor Metastasis Stealth Liposome Amino Acid Auxotrophy
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
- Allen, T.M., Hansen, C.B., and Zalipsky, S. 1995. Antibody-targeted stealth liposomes. In: Stealth Liposomes, D.D. Lasic (ed), CRC Press, Boca Raton, pp. 233–244.Google Scholar
- Bacon, G.A., Burrows, T.W., and Yates, M. 1950. The effects of biochemical mutation on the virulence of bacterium typhosum: The virulence of mutants. Br. J. Exp. Path. 31:714–724.Google Scholar
- Bacon G.A., Burrows T.W., and Yates M. 1951. The effects of biochemical mutation on the virulence of bacterium typhosum: The loss of virulence of certain mutants. Br. J. Exp. Path. 32:85–96.Google Scholar
- Baselga, J., Norton, L., Albanell, J., Kim, Y.-M., and Mendelsohn, J. 1998. Recombinant humanized anti-HER2 antibody (HerceptinTM) enhances the antitumor activity of paclitaxol and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res. 58:2825–2831.PubMedGoogle Scholar
- Bischoff, J.R., Kirn, D.H., Williams, A., Heise, C., Horn, S., Muna, M., Ng, L., Nye, J.A., Sampson-Johannes, A., Fattaey, A., and McCormick, F. 1996. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274:373–376.PubMedCrossRefGoogle Scholar
- Boucher, Y., Leunig, M., and Jain, R.K. 1996. Tumor angiogenesis and interstitial hypertension. Cancer Res. 56:4264–4266.PubMedGoogle Scholar
- Carey, R.W., Holland, J.F., Whang, H.Y., Neter, E., and Bryant, B. 1967. Clostridial oncolysis in man. Eur. J. Cancer 3:37–46.Google Scholar
- Carter, P.B., and Collins, F.M. 1974. The route of enteric infection in normal mice. J. Exp. Med. 139:1189–1203.PubMedCrossRefGoogle Scholar
- Fox, M.E., Lemmon, J.J., Mauchline, M.L., Davis, T.O., Giaccia, A.J., Minton, N.P., and Brown, J.M 1996. Anaerobic bacteria as a delivery system for cancer gene therapy: in vitro activation of 5-fluorocytosine by genetically engineered clostridia. Gene Therapy 3:173–178.PubMedGoogle Scholar
- Friedman, P.N., McAndrew, S.J., Gawlak, S.L., Trail, P.A., Brown, J.P., and Siegall, C.B. 1993. BR96 sFv-PE40, a potent single-chain immunotoxin that selectively kills carcinoma cells. Cancer Res. 53:334–339.PubMedGoogle Scholar
- Garapin A.C., Colbère-Garapin, F., Cohen-Solal, Horondniceanu, F., and Kourilsky, P. 1981. Expression of herpes simples virus type I thymidine kinase gene in Escherichia coli. Proc. Natl. Acad. Sci. USA 78:815–819.PubMedGoogle Scholar
- Gotoh, A., Ko, S.C., Shirakawa, T., Cheon, J., Kao, C., Miyamoto, T., Gardner, T.A., Ho, L.J., Cleutjens, C.B., Trapman, J., Graham, F.L., and Chung, L.W. 1998. Development of prostate-specific antigen promoterbased gene therapy for androgen-independent human prostate cancer. J. Urol. 160:220–229.PubMedGoogle Scholar
- Groisman, E.A., and Saier, M.H. Jr. 1990. Salmonella virulence: new clues to intramacrophage survival. Trends Biochem. Sci. 15:30–33.PubMedCrossRefGoogle Scholar
- Hoiseth, S.K.J., and Stocker, B.A.D. 1981. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature 291:238–239.PubMedCrossRefGoogle Scholar
- Jain, R.K. 1994. Barriers to drug delivery in solid tumors. Scientific American 271(July):58–65.Google Scholar
- Joiner, K.A. 1988. Complement evasion by bacteria and parasites. Ann. Rev. Microbiol. 42:201–230.CrossRefGoogle Scholar
- Khan, S.A., Everest, P., Servos, S., Foxwell, N., Zähringer, U., Brade, H., Rietschel, E. Th., Dougan, G., Charles, I.G., and Maskell, D.J. 1998. A lethal role for lipid A in Salmonella infections. Mol. Mircobiol. 29:571–579.Google Scholar
- King, I., Feng, M, Luo, X., Lin, S., Bermudes, D., and Zheng, L.-M. 1998. Tumor-targeted Salmonella expressing cytosine deaminase converted 5-fluorocytosine to 5-fluorouracil and inhibited tumor growth in vivo. Proc. Amer. Asoc. Can. Res. 39, p. 512, Abstract 3484.Google Scholar
- Kops, S.K., Luo, X., Fischer, J., Le, T., Bermudes, D., Bolognia, J.L., Carmichael, E., Key-Yen, A., King, I., Low, K.B., Pawelek, J.M., Sodi. S.S., and Zheng, L.-M. Salmonella typhimurium as an anti-cancer vector: Localization within solid tumors. Proc. Amer. Asoc. Can. Res. 38, p. 7, Abstract 46.Google Scholar
- Lemmon, M.J., van Zijl, P., Fox, M.E., Mauchline, M.L., Giaccia, A.J., Minton, N.P., and Brown, J.M. 1997. Anaerobic bacteria as a gene delivery system that is controlled by the tumor microenvironment. Gene Therapy 4:791–796.PubMedCrossRefGoogle Scholar
- Low, K.B., Ittensohn, M., Le, T., Platt, J., Sodi, S., Amoss, M., Ash, O., Carmichael, E., Chakraborty, A., Fischer, J., Lin, S.L., Luo, X., Miller, S.I., Zheng, L.-M., King, I., Pawelek, J.M., and Bermudes, D. 1998. Disruption of the Salmonella msbB gene suppresses virulence and TNFα induction yet retain tumor-targeting in vivo. Proc. Amer. Asoc. Can. Res. 39, p. 60, Abstract 409.Google Scholar
- Möse, J.R., and Möse, G. 1964. Oncolysis by Clostridia. I. Activity of Clostridium butyricum (M-55) and other nonpathogenic clostridia against the Ehrlich carcinoma. Cancer Res. 24:212–216.Google Scholar
- Parker, R.C., Plummer, H.C., Siebenmann, C.O., and Chapman, M.G. 1967. Effect of histollyticus infection and toxin on transplantable mouse tumors. Proc. Soc. Exp. Biol. Med. 66:461–467.Google Scholar
- Pawelek, J., Low, K.B., and Bermudes, D. 1997. Tumor-targeted Salmonella as a novel anti-cancer vector. Cancer Research 57:4537–4544.PubMedGoogle Scholar
- Siegall, C.B. 1995. Targeted therapy of carcinomas using BR96 sFv-PE40, a single-chain immunotoxin that binds to the Le(y) antigen. Semin Cancer Biol. 6:289–295.PubMedCrossRefGoogle Scholar
- Trail, P.A., Willner, D., Lasch, S.J., Henderson, A.J., Hostead, S., Casazaza, A.M., Firestone, R.A., Hellström, I., and Hellström, K.E. 1993. Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261:212–215.PubMedGoogle Scholar
- Zheng, L.-M., Luo, X., Fischer, J., Le, T., Bermudes, D., Low, B., Pawelek, J.M., and King, I. 1997. Attenuated Salmonella typhimurium inhibited tumor metastasis in vivo. Proc. Amer. Asoc. Can. Res. 38, p. 9, Abstract 60.Google Scholar
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© Kluwer Academic Publishers 2002