Clostridium spores for tumor-specific drug delivery.
Insufficient blood supply of rapidly growing tumors leads to the presence of hypoxia, a well-known feature in solid tumors. Hypoxia is known to decrease the efficiency of currently used anti-cancer modalities like surgery, chemotherapy and radiotherapy. Therefore, hypoxia seems to be a major limitation in current anti-cancer therapy. The use of non-pathogenic clostridia to deliver toxic agents to the tumor cells takes advantage of this unique physiology. These strictly anaerobic, Gram-positive, spore-forming bacteria give, after systemic administration, a selective colonization of hypoxic/necrotic areas within the tumor. Moreover, they can be genetically modified to secrete therapeutic proteins like cytosine deaminase or tumor necrosis factor-alpha. The specificity of this protein delivery system can be further increased when expression is controlled by the use of a radio-inducible promoter, leading to increased spatial and temporal regulation of protein expression. This approach of bacterial vector systems to target protein expression to the tumor can be considered very safe since bacteria can be eliminated at any moment by the addition of proper antibiotics. The Clostridium-based delivery system thus presents an alternative therapeutic modality to deliver anti-tumor agents specifically to the tumor site. This high selectivity offers a major advantage in comparison with the classical gene therapy systems.
Nuyts
S
S
Laboratory of Bacteriology, Rega Institute, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. Sandra.Nuyts@uz.kuleuven.ac.be
Van Mellaert
L
L
Theys
J
J
Landuyt
W
W
Lambin
P
P
Anné
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D015687:Cell Hypoxia; D003013:Clostridium / Q000235:genetics* / Q000502:physiology; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000528:radiation effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D013171:Spores, Bacterial / Q000235:genetics
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins