C. novyi-NT

Tumor-fighting Bacteria
Despite significant research, cancer remains a lethal disease. BioMed Valley Discoveries (BVD) is studying a new way to combat cancer—one that exploits the unusual conditions inside the tumor using tumor-fighting bacteria.

Tumor Growth
Tumors form when small clusters of cancerous cells deceive the body into continuously feeding them. These malignant cells produce proteins that promote the growth of blood vessels, which provide the tumor with oxygen and energy that support further growth.

Eventually, tumor growth can outpace the ability of blood vessels to keep up with the tumor’s needs. While tumors continue to grow and expand, some regions within the tumors become starved of oxygen (hypoxic) and nutrients, and start to grow more slowly, lie dormant, or die (become necrotic). Hypoxic, slow-growing, and necrotic tumor cells are often resistant to radiation therapy and chemotherapy. However, these cells form an ideal environment for anaerobic bacteria that thrive in low oxygen conditions but stop growth abruptly or are killed in high oxygen or aerobic conditions.

The Enemy of My Enemy
To be clinically effective, cancer drugs cannot leave any malignant, even dormant, cells behind because these cells still have the potential to reactivate and drive tumor growth. Currently, very little can be done to destroy completely hypoxic tumor cells. Research in mice and other animals has shown that anaerobic bacteria seek out low-oxygen environments and destroy tumor cells in the area while leaving well-oxygenated tissue unharmed. After the tumor-fighting bacteria have destroyed cancer cells, the bacteria can be controlled by commonly available antibiotics. BioMed Valley Discoveries is researching the effects of one of these types of bacteria in patients with inoperable tumors.

Bugs illustration by Katie Vicari

Research with Deep Roots
It’s an unconventional approach to take someone with one disease and infect that person with another potential illness. However, this type of cancer treatment has deep scientific roots.

As long ago as the 1890s, a doctor named William B. Coley discovered a curious fact: Occasionally, cancer patients who underwent surgery and developed a bacterial infection afterward became completely cured of their tumors. In the nineteenth century, scientists didn’t have the tools to understand fully the significance of this finding, but Coley’s work nevertheless got people thinking about the potential of bacteria to treat illnesses like cancer.

It wasn’t until over a half-century later, though, in the 1950s and 1960s, that researchers tried using an anaerobic bacterium, Clostridium butyricum (C. butyricum), to fight cancer. This method worked. C. butyricum destroyed large portions of tumors in treated patients. However, the method had a considerable problem. Scientists at the time could not adequately control the bacteria. While the bacteria were susceptible to antibiotics, they still produced toxins that made patients sick. The use of anaerobic bacteria to treat tumors was put on hold while radiation and chemotherapy emerged as standard treatments.

In the early 2000s, Bert Vogelstein’s laboratory at Johns Hopkins University returned to the study of bacteria as a possible treatment for cancer. The lab weakened a strain of Clostridium novyi by removing a lethal toxin. They called this bacterium Clostridium novyi-NT (C.novyi-NT). Researchers then began using C. novyi-NT in mice and other animals to see if it could treat tumors and if there were any undesired effects from the bacterium itself.

Research by Bert Vogelstein’s laboratory and BVD has shown that 30% of animals treated with spores of the weakened C. novyi-NT showed a dramatic reduction in tumor size. In addition to destroying tumor cells, the bacteria may have provoked the animal’s immune system to attack cancer cells.

Our Goal: To Destroy Tumors
BioMed Valley Discoveries aims to create a new generation of cancer drugs by using the Vogelstein Laboratory’s promising research as a starting point. Researchers at BVD have advanced C. novyi-NT to Phase I clinical trials. The aim of these trials is to evaluate the safety of C. novyi-NT and to determine the appropriate dose to use as a single therapy or in combination with another therapy. While many years of challenging work remain, the initial results show promise. BVD’s hope is that this work will someday lead to a new class of therapies to combat cancer, one of the world’s deadliest illnesses.

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