Researchers in the US have successfully shrunk cancer tumors in rats, dogs and now one human patient, by directly injecting the tumors with a modified version of Clostridium novyi (C. novyi-NT) to trigger strong and precisely targeted anti-cancer responses.

The team, including researchers from Johns Hopkins Kimmel Cancer Center in Baltimore, MD, writes about the work in the journal Science Translational Medicine.

The revelation that bacteria like Clostridium can be used to treat cancer is not new. For instance, the Clostridia Research Group (CRG) has been working in this area since it was set up in 2004 by Prof. Nigel Minton at Nottingham University in the UK.

The bacterium thrives in oxygen-poor environments, like those in the center of solid tumors. Prof. Minton explained at a conference in 2011 that because of this natural feature of the bacterium - which is "exquisitely specific" and needs no fundamental alterations - it kills tumor cells but leaves healthy tissue unscathed.

Bacteria attack oxygen-starved tumor cells

Shibin Zhou, associate professor of oncology at Johns Hopkins Kimmel Cancer Center and senior author of the new study, together with other colleagues at Johns Hopkins, has also been working on the anti-cancer properties of Clostridium, and C. novyi in particular, for the past 10 years.

They first became interested when they observed that some cancer patients who contract serious bacterial infections appear to show cancer remission.

They focused on soft tissue tumors because they are often locally advanced and have spread to normal tissue. And like the group in the UK, they were interested in the fact the bacteria cannot germinate in normal tissue and will only attack oxygen-starved tumor cells.

Also, Prof. Zhou explains, the "advantage of using bacteria to treat cancer is that you can modify these bacteria relatively easily, to equip them with other therapeutic agents, or make them less toxic as we have done here."

In its natural form, C. novyi is found in the soil and can cause an infection that damages tissue in cattle, sheep and humans. Before they used it, the researchers removed one of the bacterium's toxin-producing genes to make it into a safer form called C. novyi-NT.

Bacteria eradicated and shrank tumors without harming healthy tissue

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C. novyi-NT germination gram stain in dog tumor. The bacteria are darker and rod-shaped.
Image credit: David L. Huso and Baktiar Karim, Johns Hopkins Department of Pathology.

For their study, they injected C. novyi-NT spores directly into naturally occurring tumors in 16 pet dogs. Six of the dogs showed an anti-tumor response within 21 days of their first injection.

The tumors were completely eradicated in three of the six responsive dogs, and in the other three dogs, the tumors shrank by at least 30% (measured along the longest diameter of the tumor).

The team notes that most of the dogs experienced fever, tumor abscesses and inflammation, side effects that normally accompany bacterial infection.

The researchers also tested the effect of injecting C. novyi-NT spores into a female patient with an advanced soft tissue tumor in the abdomen. They gave the spore injection direcly into a metastatic tumor in her arm.

The result was significant reduction in tumor size in and around the bone. But the team notes because this was a phase 1 trial in one patient, they cannot be sure if the same range of responses they saw in the dogs can happen in humans.

In another phase of the study, the researchers also tested the spore injection in rats with implanted gliomas, a type of brain tumor.

When they examined the tumors and brain samples under a microscope, they found the bacteria had killed tumor cells without harming healthy tissue that was only micrometers away.

The treated rats also lived longer than untreated rats - surviving 33 days compared with 18 days after treatment.

The reason the researchers chose to treat dogs as well as rats in the study is because dogs have many genetic similarities to humans, and many dogs with cancer are given the same treatment as that given to humans.

Prof. Zhou says they have continued to study the effect of the spore injection in humans and are waiting for final results:

"We expect that some patients will have a stronger response than others, but that's true of other therapies as well. Now, we want to know how well the patients can tolerate this kind of therapy."

Potential to combine with traditional cancer therapies

Other researchers have already been looking at combining chemotherapy with C. novyi-NT treatment and testing the effect in mice. Traditional therapies like chemotherapy and radiation increase the amount of oxygen-poor tissue in the tumor, which can then make the spore treatment more potent and effective.

"Another good thing about using bacteria as a therapeutic agent is that once they're infecting the tumor, they can induce a strong immune response against tumor cells themselves," adds Prof. Zhou.

Although they have yet to see this in the dog and human studies, he notes that it may be possible, as previous work on mice suggests that the spore treatment helps to create a sustained anti-tumor response in the immune system, one that lingers long after the initial bacteria treatment has finished.

The study follows other recent news of a fast, low-cost way of making anti-cancer molecules that imitate the body's natural anti-cancer mechanisms.