Skip to main content
SpringerLink
Log in

Tumor-Targeted Salmonella

Highly Selective Delivery Vectors

  • Chapter
  • First Online:
Cancer Gene Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 465))

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

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.

    CAS  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.

    CAS  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.

    CAS  PubMed  Google 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. Science274:373–376.

    Article  CAS  Google Scholar 

  • Boucher, Y., Leunig, M., and Jain, R.K. 1996. Tumor angiogenesis and interstitial hypertension. Cancer Res.56:4264–4266.

    CAS  PubMed  Google Scholar 

  • Carey, R.W., Holland, J.F., Whang, H.Y., Neter, E., and Bryant, B. 1967. Clostridial oncolysis in man. Eur. J. Cancer3:37–46.

    Article  Google Scholar 

  • Carter, P.B., and Collins, F.M. 1974. The route of enteric infection in normal mice. J. Exp. Med.139:1189–1203.

    Article  CAS  Google 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 Therapy3:173–178.

    CAS  PubMed  Google 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.

    CAS  PubMed  Google 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. USA78:815–819.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

  • Groisman, E.A., and Saier, M.H. Jr. 1990. Salmonella virulence: new clues to intramacrophage survival. Trends Biochem. Sci.15:30–33.

    Article  CAS  Google Scholar 

  • Hoiseth, S.K.J., and Stocker, B.A.D. 1981. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature291:238–239.

    Article  CAS  Google Scholar 

  • Jain, R.K. 1994. Barriers to drug delivery in solid tumors. Scientific American271(July):58–65.

    Article  CAS  Google Scholar 

  • Joiner, K.A. 1988. Complement evasion by bacteria and parasites. Ann. Rev. Microbiol.42:201–230.

    Article  CAS  Google 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.

    Article  CAS  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 Therapy4:791–796.

    Article  CAS  Google 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.

    Article  Google Scholar 

  • Pawelek, J., Low, K.B., and Bermudes, D. 1997. Tumor-targeted Salmonella as a novel anti-cancer vector. Cancer Research57:4537–4544.

    CAS  PubMed  Google 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.

    Article  CAS  Google 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. Science261:212–215.

    Article  CAS  Google 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 

Download references

Author information

Authors and Affiliations

  1. Vion Pharmaceuticals, Inc., 4 Science Park, New Haven, Connecticut, 06511, USA

    David Bermudes

  2. Department of Therapeutic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06520, USA

    Brooks Low

  3. Department of Therapeutic Dermatology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06520, USA

    John Pawelek

Authors
  1. David Bermudes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brooks Low
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Pawelek
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Imperial College School of Medicine, Hammersmith Hospital, London, UK

    Nagy A. Habib

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic Publishers

About this chapter

Cite this chapter

Bermudes, D., Low, B., Pawelek, J. (2002). Tumor-Targeted Salmonella . In: Habib, N.A. (eds) Cancer Gene Therapy. Advances in Experimental Medicine and Biology, vol 465. Springer, New York, NY. https://doi.org/10.1007/0-306-46817-4_6

Download citation

  • DOI: https://doi.org/10.1007/0-306-46817-4_6

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-306-46191-0

  • Online ISBN: 978-0-306-46817-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation