Toxic bacteria safely shrinks cancer

 The modified version of Clostridium novyi bacterium produced strong and precisely targeted results in cancers in rats, dogs, and now a human subject, scientists report.

Before injecting spores into tumors in test subjects, researchers removed one of the bacterium’s toxin-producing genes to make it safer for therapeutic use, though it still caused side effects.

“One 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,” says Shibin Zhou, associate professor of oncology at Johns Hopkins Kimmel Cancer Center.

In its natural form, C. novyi is found in the soil and can contaminate open wounds and cause tissue-damaging and potentially fatal infection in grazing animals and humans.

The microbe thrives only in oxygen-poor environments. That makes it suitable for destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation; at the same time, it spares nearby healthy, oxygen-rich tissue.

For a new study published in Science Translational Medicine, researchers tested direct-tumor injection of modified C. novyi spores in 16 pet dogs being treated for naturally occurring tumors. Within 21 days, tumors were eradicated in three dogs and shrunk by at least 30 percent in three others.

Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation.

In a Phase I clinical trial at MD Anderson Cancer Center, a patient with an advanced soft tissue tumor in the abdomen received the spore injection directly into a metastatic tumor in her arm. The treatment significantly reduced the tumor in and around the bone, but with side effects similar to those the dogs experienced.

Zhou and colleagues began exploring C. novyi’s cancer-fighting potential more than a decade ago after studying hundred-year-old accounts of an early immunotherapy called Coley toxins. That treatment evolved from the observation that some cancer patients with serious bacterial infections showed cancer remission.

Verena Staedtke, a Johns Hopkins neuro-oncology fellow, first tested the spore injection in rats with implanted brain tumors called gliomas. Microscopic evaluation of the tumors showed that the treatment killed tumor cells but spared healthy cells just a few micrometers away.