Bacteria Used in Cancer Treatment

Laura Jassowski
5/19/11





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Clostridium
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Heliobacter pylori



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C. novyi-NT



Abstract: Research has shown that bacteria has been used successfully in treating cancer in patients. Many patients’ resistance to cancer has prompted scientists to search for alternative methods of treating cancer. Many different bacterial species have been studied as either a vector to deliver the tumoricidal medicine into the tumor or as live genetically modified bacteria designed to replicate inside the tumor and kill it. Although many of the different approaches have proven successful and look very promising, they still need to be investigated slightly more before they can be applied conventionally.

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William Coley

Introduction and Backround: In a world riddled with cancer, where the body’s own cells are the disease, there are few effective treatments available for the patients afflicted with the disease. Some of the cancers don’t respond to conventional treatment. This has prompted scientists to look for a better way to deliver medicine into the tumor and kill it without harming the patient’s healthy living tissue around it. Scientists started looking to the world of microbiology for the answer to their problems. The discovery of bacteria as an anticancer was discovered about one hundred years back. The German physicians W. Busch and F. Fehleisen separately observed that certain cancers went into regression when their patients accidentally became infected with erysipelas (Streptococcus pyogenes). Independently, American physician William Coley noticed that his patient’s neck cancer began to regress when he contracted the same infection (Bacteria in Cancer Therapy, Patyar, S). Coley began the first well- documented use of bacteria to treat cancer. He developed a vaccine in the 1800’s that comprised of two killed bacterial species, S.pyogenes and Serraita marcescens to stimulate the infection without the risk of the fever. This vaccine was widely used to treat all kinds of cancers- sarcomas, carcinomas, lymphomas. Complete, prolonged regression was documented in many cases. This research sets the groundwork for anticancer research with bacteria today.






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Schematic overview of role of bacteria in cancer therapy

Using Bacteria as Tumorcides: The first way scientists are trying to develop bacteria into cancer treatments are as a tumorcide (Bacteria Successful in Cancer Treatment, Science Daily). Certain species of anaerobic bacteria, especially from the genus Clostridium, have proven to consume oxygen poor tumor tissue and thrive inside their anaerobic environments (Bacteria in Cancer Therapy, Patyar, S). The only problem is the bacteria die when they come into contact with the oxygen rich tissue of the tissue, and don’t completely consume the tumor. Scientists then need to combine with other treatments to finish off the tumor. There is tumor regression, but there is also a high degree of toxicity associated with such a pathogenic bacteria and the animal falls ill or dies. Scientists have tried shifting their focus to a nonpathogenic form of Clostridium –M55 (Bacteria in Cancer Therapy, Patyar, S). The problem with this bacterium is it was able to colonize but there was little cancer regression. Scientists then took Clostridium novyi and combined it with chemotherapeutic agents. This strategy is known as COBALT (combination bacteriolytic therapy) (Bacteria in Cancer Therapy, Patyar, S). This resulted in significant anti-tumor properties but still resulted in animal deaths. This bacterium was exploited because of its membrane disrupting potential. This process will be exploited further and it has proved promising because of its significant eradication of tumors in mice. To make poorly vascularized regions of the tumor accessible, it is used in conjunction with anti-microbial agents.

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Using Bacteria as a Vector: Another method is using bacteria as a vector instead of a tumorcide (Bacteria Successful in Cancer Treatment, Science Daily). To overcome many of the problems faced with the previous experiments, scientists are using genetically modified bacteria as vectors to deliver therapy directly to a tumor. To do this, scientists produce a protein of interest specifically in the tumor microenvironment and then provide strong therapy to various cancer treatments. One example is since S.Typhimurium naturally colonizes in the liver and in it's attenuated form could be used to deliver cytokines directly locally to liver to effect hepatic metastases. (Bacteria in Cancer Therapy, Patyar, S).
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Enzume Structure


Bacteria and Enzymes: Still another way for bacteria to be utilized to help treat cancer is bacterially directed enzyme producing therapy. This form overcomes the acceptable side effects of bacterial therapy and uses anaerobic bacteria that have been transformed with enzymes to convert a non-toxic prodrug into a toxic drug. The enzyme from the bacteria is solely expressed in the tumor. Although combinations of enzymes and prodrugs have killed tumors in vitro, so far live results have been disappointing (Bacteria in Cancer Therapy, Patyar, S).


Problems and Conclusion: Although the results of many of the tests from all of the many different ways to use bacteria to treat cancer have been promising and bear further research, there are some problems. The first is the toxicity of the bacteria at the dose required for therapeutic use. If the dose is lowered it reduces efficiency. There is also the risk of developing a systemic infection from the injected bacteria. Another problem is even the removal of toxic genes like in COBALT therapy still leads to fifteen to forty- five percent mortality in mice(Bacteria in Cancer Therapy, Patyar, S).. There is also the issue of incomplete lysis of the tumor. Despite these setbacks, using bacteria to treat cancer may be a promising field of research for the future.





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Citation:

"Bacteria Successful in Cancer Treatment." BioScholar News : Latest Biology, Health, Science & Technology Articles. BioScholar, 06 Sept. 2007. Web. 12 May 2011. http://news.bioscholar.com/2007/09/bacteria-successful-in-cancer-treatment.html.

Patyar, S., R. Joshi, D. S. Prasad Byrav, and And Others. "Bacteria in Cancer Therapy: a Novel Experimental Strategy." PubMed Central. Journal of Biomedical Science, 23 Mar. 2010. Web. 10 May 2011.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854109/.

"SGM : News : Media Releases." SGM.ac.uk : Society for General Microbiology. Society For General Microbiology, 06 Sept. 2007. Web. 10 May 2011. https://www.sgm.ac.uk/news/releases/edi0714.cfm.

Society for General Microbiology. "Bacteria Successful In Cancer Treatment." ScienceDaily, 9 Sep. 2007. Web. 17 May 2011.