Use of bacteria as anticancer agents.
Historically, bacteria were used as oncolytic agents for malignant brain tumours. Advances in bacteriology and molecular biology have widened the scope of bacterial approaches to cancer therapy and various possibilities include the use of bacteria as sensitising agents for chemotherapy, as delivery agents for anticancer drugs, and as vectors for gene therapy. Bacterial toxins can be used for tumour destruction and cancer vaccines can be based on immunotoxins of bacterial origin. The most promising approaches are the use of genetically modified bacteria for selective destruction of tumours, and bacterial gene-directed enzyme prodrug therapy. Knowledge gained from study of bacterial genomes forms an important basis of use of bacteria as anticancer agents. TAPET (Tumour Amplified Protein Expression Therapy) uses a genetically altered strain of Salmonella as a bacterial vector, or vehicle, for preferentially delivering anticancer drugs to solid tumours. Verotoxin 1 (VT1) of Escherichia coli has been used for ex vivo purging of human bone marrow of cancer cells before autologous bone marrow transplant. E. coli genes and enzymes have become part of well-known prodrug approaches to cancer in which inert prodrugs can be converted in vivo to highly active species. IL-4 fused with Pseudomonas exotoxin has been administered directly into malignant brain tumours and binds with high affinity to IL-4 receptors, which do not exist on normal brain cells, thus destroying a major part of the tumour without harming the normal brain tissue. It is in Phase I/II clinical trials in patients with glioblastoma. No ideal anticancer agent of bacterial origin that is applicable to all types of cancers has been discovered yet. The most promising approach to malignant brain tumours appears to be the use of genetically engineered bacteria that destroy the tumour selectively while sparing the normal brain tissue.
Jain
K K
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Jain PharmaBiotech, Bläsiring 7, CH-4057 Basel, Switzerland. jain@pharmabiotech.ch
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D001419:Bacteria / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D043525:Cytosine Deaminase; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D016680:Genome, Bacterial; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D009601:Nitroreductases / Q000235:genetics; D009700:Nucleoside Deaminases / Q000235:genetics; D011355:Prodrugs / Q000494:pharmacology; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D009601:Nitroreductases; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase