Chapter 24. Clostridium-Mediated Transfer of Therapeutic Proteins to Solid Tumors

  1. David T. Curiel M.D. and
  2. Joanne T. Douglas Ph.D.
  1. Philippe Lambin M.D., Ph.D.1,
  2. Jan Theys Ph.D.1,
  3. Sandra Nuyts M.D.2,
  4. Willy Landuyt Ph.D.3,
  5. Lieve Van Mellaert Ph.D.4 and
  6. Jozef Anné Ph.D.4

Published Online: 31 MAR 2003

DOI: 10.1002/0471234303.ch24

Vector Targeting for Therapeutic Gene Delivery

Vector Targeting for Therapeutic Gene Delivery

How to Cite

Lambin, P., Theys, J., Nuyts, S., Landuyt, W., Van Mellaert, L. and Anné, J. (2002) Clostridium-Mediated Transfer of Therapeutic Proteins to Solid Tumors, in Vector Targeting for Therapeutic Gene Delivery (eds D. T. Curiel and J. T. Douglas), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/0471234303.ch24

Editor Information

  1. Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, The University of Alabama at Birmingham, USA

Author Information

  1. 1

    Department of Radiation Oncology, RTIL/U.H. Maastricht, The Netherlands

  2. 2

    Laboratory of Bacteriology, Rega Institute and Department of Radiation Oncology, Laboratory of Experimental Radiobiology, K. U. Leuven, Leuven, Belgium

  3. 3

    Department of Radiation Oncology, Laboratory of Experimental Radiobiology, K.U. Leuven, Belgium

  4. 4

    Laboratory of Bacteriology, Rega Institute, K.U. Leuven, Belgium

Publication History

  1. Published Online: 31 MAR 2003
  2. Published Print: 9 AUG 2002

ISBN Information

Print ISBN: 9780471434795

Online ISBN: 9780471234302

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Keywords:

  • Clostridium;
  • tumor;
  • hypoxia;
  • gene transfer;
  • radio-induction;
  • anti-cancer treatment;
  • gene-therapy

Summary

The presence of severe hypoxia and necrosis in solid tumors limits the efficacy of conventional treatment modalities. On the other hand, this unique physiology offers the potential to apply an anaerobic bacterial transfer system in cancer treatment. Systemically administered spores of non-pathogenic Clostridium bacteria specifically germinate into metabolically active cells in the hypoxic/necrotic regions of tumors. These clostridial cells can be genetically engineered to express and secrete therapeutic proteins such as cytosine deaminase or tumor necrosis factor a. The use of this alternative and innovative approach offers several advantages over classical gene therapy systems, including its high tumor-specificity. Selectivity can even be improved by the use of radio-inducible promoters offering spatial and increased temporal control of gene expression. Taken together, the data described here provide evidence for the potential application of Clostridium-based therapeutic protein transfer to tumors in anti-cancer therapy.