Doctors use bacteria as a weapon against cancer

This is a perfect case of my enemy's enemy is my friend.

A small potentially dangerous bacterium appears to target malignant cells and could be a new way to fight cancer, according to a small preliminary study report.

Clostridium novyi-NT bacteria can cause gaseous gangrene and sepsis if the infection is triggered in a wound.

But when injected into a tumor, Clostridium novyi-NT appears to both directly attack cancer and encourage the body's immune response against cancer cells, said Dr. Filip Janku , principal investigator. He is an associate professor in the Department of Experimental Cancer Therapy at the MD Anderson Cancer Center of the University of Texas, Houston.

"The patients have only been exposed to the bacteria for a week, but even with this limited exposure, we have found some interesting activity and, in some patients, clinically significant," said Janku.

Clostridium novyi has been associated with a human disease. In 2000, the United States Centers for Disease Control and Prevention reported that a handful of drug addicts in the United Kingdom fell ill or died after its injection sites became infected with the bacteria.

The strain used in this clinical trial, Clostridium novyi-NT, has been weakened to prevent it from producing its toxin, which can be deadly to humans, Janku said. NT means "nontoxic".

Clostridium novyi thrives in oxygen-poor environments. The researchers thought this could make the bacteria a prime candidate for cancer control by concentrating the infection on the site of the tumor.

"Normal tissues, even if they are poor in oxygen, always have enough oxygen so that these bacteria can not germinate and proliferate," Janku said. "The cancerous tissue is low in oxygen, most often at the center of cancer."

To test whether the bacteria could help fight cancer, the researchers injected tumors of 24 patients with a single dose of Clostridium novyi-NT, ranging from 10,000 to 3 million spores.

Fifteen patients had sarcoma, two patients had melanoma and seven had a variety of cancers, the researchers said.

Scientists expected Clostridium novyi-NT to help fight the tumor in two ways.

First, the bacterial infection itself could cause the direct destruction of tumor cells, said Janku.

"If that happens, it actually helps to increase the presence of tumor-specific antigens, which are proteins that make a tumor more obvious to the immune system," said Janku. "It can stimulate the immune system to attack cancer."

Bacteria could also activate the immune system to fight cancer, even if the infection does not kill tumor cells, Janku added.

Patients participating in this clinical trial were infected with a bacterial infection for one week, then antibiotics were administered to everyone, to kill Clostridium novyi-NT, said Janku.

"Clostridium is actually pretty sensitive to antibiotics," noted Janku.

Bacteria germinated in the cancers of 11 of 24 patients, leading to the death of the tumor cells.

Tumor contraction greater than 10% was observed in 23% of patients. However, Janku said that this could be an underestimate, since the infection causes inflammation of the surrounding tissues, giving the impression that the lesion is larger than that. she is not really.

After bacterial treatment, the cancer stabilized in 21 patients. The researchers reported that when both injected and non-injected lesions were included, the stable disease rate was 86%.

The potential of Clostridium novyi-NT to elicit an immune response against cancer is intriguing, said Sacha Gnjatic, associate director of the Mount Sinai Human Immunity Surveillance Center in New York.

"This is where the promise of this type of therapy lies.You would expect the injected lesion to produce some kind of response because you disrupt the tumor cells," Gnjatic said. "What would be interesting is that it could trigger an immune response that could eventually support uninjected tumors.It is the holy grail of immunotherapy."

Janku said he was particularly excited about the bacteria's ability to fight against sarcomas, bone, muscle and soft tissue cancers.

"The classic immunotherapy that is now approved or that is the subject of much research does not seem to work for the majority of sarcomas," explained Janku.

The researchers moved on to the next phase, during which patients taking pembrolizumab (Keytruda), an immunotherapy drug, will also be treated with a single injection of Clostridium novyi-NT, Janku said. The researchers suspect that the two therapies combined will create a strong immune response against cancer.

However, they will need to monitor the potential side effects of Clostridium novyi-NT, Janku added.

Two patients treated with the highest dose of 3 million Clostridium novyi-NT spores became ill and had sepsis and / or gas gangrene, which led the researchers to set the maximum tolerated dose at 1 million spores.

The researchers also found the bacteria in the blood of two patients, which means that the infection will have to be followed closely, said Janku.

"This did not translate into the seeding of Clostridium anywhere other than in the injected area, but it is a theoretical possibility since we were able to detect it in the blood culture. one or two patients, "said Janku.

Patients might also be sensitive to the side effects of the immune response, such as low blood pressure or fever, he added.

The test results were to be presented Sunday at the International Conference on Cancer Immunotherapy, in New York. The meeting is sponsored jointly by the Institute for Cancer Research, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology and the Association. American for cancer research.

Research presented at meetings should be considered preliminary until published in a peer-reviewed journal.