Fighting cancer with bacteria

Mouse tumors treated with Clostridium novyi: From Bettegowda et al, PNAS 100:15803

I just got back from the annual American Society of Microbiology Conference on Undergraduate Education, which ended with a fascinating plenary talk given by Bert Vogelstein, of Johns Hopkins University. Prof. Vogelstein has received many academic honors over his career, and currently has the distinction of being the most highly cited scientist in the life sciences today. That is, the scientific papers on which he is an author have been cited by other researchers in their papers more than any other scientist.

The talk detailed recent work on the use of Clostridium novyi, an organism associated with infrequent human infections, but unlike other Clostridium species, has an extremely strict anaerobic growth requirement. The growth of solid mass tumors is promoted by the development of blood vessels, which enable the delivery of nutrients and oxygen to the tumor mass. The new blood vessels, however, supply the exterior of the tumor, and the interior of the tumor frequently has very little blood supply, and consequently very low to non-existent oxygen levels.

This observation offers a novel way to approach tumor therapy. Most standard methods of cancer treatment are via surgical resection of the tumor, or radiation/chemical treatments to inhibit or kill the fast growing cancer cells. Some new methods (for example, Avastin) work instead to inhibit the development of new blood vessels, in essence starving the tumor cells. The drawbacks of all of these methods is that they will significantly affect the normal cells of the body, and consequently cancer treatment is typically a harsh process on the patient.

With Clostridium novyi, we have an organism that grows only in anaerobic conditions, such as those in the interior of a solid mass tumor. The premise is this: a patient is purposefully infected with endospores from C. novyi, which unlike the vegetative cells, are able to tolerate oxygen. When the endospores get to an environment appropriate for growth (for example, in the interior of a tumor,) the endospores germinate and begin to grow. Many species of Clostridium also produce a variety of toxins that can damage and destroy human cells, and the administration of C. novyi in combination with other antitumor compounds, causes the rapid destruction of the tumor as the tumor is destroyed from within.

The main complication here is sepsis, or infection of the blood as growth of the bacterium spreads throughout the body. The clever bit here is that C. novyi is exquisitely sensitive to penicillin, so that once the patient begins to show the signs and symptoms of sepsis such as spiking fever, the patient can be treated with common antibiotics to bring the infection under control.

 

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About ycpmicro

My name is David Singleton, and I am an Associate Professor of Microbiology at York College of Pennsylvania. My main course is BIO230, a course taken by allied-health students at YCP. Views on this site are my own.

Posted on June 6, 2011, in Microbes in the News, Strange but True and tagged , , , . Bookmark the permalink. 2 Comments.

  1. Kristina sprenkle

    I never knew that we can cure some tumors with baceria. With health care theses days it seems to be a nicer but less espensive then going through a very expensive procedure. This also seems to be a more natural procedure unless you have a reaction to the introduced bacteria or to the antibiotics that are used to control the useful bacteria. whether it is better at removing all of the tumor is unsure. Some tumors cannot be removed completely and do we know if this bacteria removes all of the tumors?? It would also be interesting to compare how many tumors return either after the surgery and after bacteria to see which one as the lower reoccurrences of the tumor.

  2. I should stress that the above treatment regimen has only been successfully done with dogs to treat tumors. Dr. Vogelstein described these experiments in his talk, and I inferred that they were pets that had cancer, and this was offered to the pet owners as an opportunity to learn whether a novel treatment had promise in a clinical setting. Dr. Vogelstein reported that in almost all cases the tumor mass greatly decreased in size as the bacterial infection progressed, and that the bacteria were brought under control with appropriate antibiotic treatment. One type of cancer appeared to be unresponsive to this method, and that was osteosarcoma, or cancer of the bone. Dr. Vogelstein hypothesized that this was possibly due to the atypical blood supply of the bone matrix, and perhaps the bacterium was unable to access the mass of the tumor.

    He also reported that two humans have undergone a very preliminary test with this method, but it was not to treat cancer, it was only to see how rapidly C. novyi is cleared from the system following antibiotic treatment. Both people were immediately put onto antibiotics when they spiked a fever, and this time frame is far too short of the anti-tumor activities to have an effect. Much further animal and initial human testing is necessary, but regardless it is a fascinating approach to treating cancers.

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