Direct, intratumoral injection of spores of a weakened strain of the anaerobic bacterium Clostridium novyi prolonged survival in rats with glioma and produced an objective response in six dogs and a human patient with soft-tissue sarcomas.

In the late 1890s, a bone surgeon in New York City noticed that cancer patients who developed postsurgical bacterial infections had better outcomes than those who didn't. Since then, researchers have been chasing the idea of using bacteria to treat cancer—especially hypoxic cells deep within a tumor that are difficult to treat with chemotherapy or radiation.

That strategy received a boost recently from a study showing that intratumoral injection of spores of an anaerobic bacterium prolonged survival in rats with gliomas and produced objective responses in dogs and a human patient with soft-tissue sarcomas.

“Rodent models of cancer often let us down in the clinic, as the results are oftentimes not translated to humans,” says cancer geneticist Saurabh Saha, MD, PhD, the study's lead investigator and president of BioMed Valley Discoveries in Kansas City, MO, which sponsored the research. To bridge the gap between rodents and humans, the researchers enlisted pet dogs with naturally occurring soft-tissue sarcomas, which have clinical and histopathologic features similar to soft-tissue sarcomas in humans.

Saha and his collaborators injected 100 million spores of Clostridium novyi-NT, a weakened strain of C. novyi, directly into the tumors of 16 pet dogs. The dogs received up to four treatments, given once a week. Three dogs experienced complete responses and three experienced partial responses, the researchers reported in Science Translational Medicine.

The researchers then launched a phase I investigational trial. The first patient to enroll in the trial was a 53-year-old woman with metastatic leiomyosarcoma who had undergone surgery and multiple chemotherapy and radiation treatments. The researchers injected a tumor in her shoulder with 10,000 spores of C. novyi-NT, causing a painful infection and fever. A biopsy taken 4 days later showed a significant reduction in tumor size and no viable tumor cells. However, the patient died 6 months after therapy due to disease progression in noninjected tumors.

The goal, says Saha, is to find a way to treat cancer's spread. “Because most cancer patients die of metastatic disease,” he notes, “we have to further optimize the therapy to treat noninjected tumors and metastatic disease for this therapy to be maximally effective.” Immune checkpoint inhibitors, for example, might enhance treatment of noninjected tumors, he says.