Dangerous bacteria could be used 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.

The bacteria, Clostridium novyi-NTcan cause gaseous gangrene and sepsis if the infection is allowed to break loose in a wound.

But when injected into a tumor, Clostridium novyi-NT appears to both directly attack the cancer and encourage the body's immune response against cancer cells, said lead researcher, Dr. Filip Janku.

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 linked to the human disease. In 2000, the US Centers for Disease Control and Prevention reported that a handful of drug addicts in the UK had fallen ill or died after its injection sites had been contaminated with the bacteria.

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

Clostridium novyi flourishes in low oxygen 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 a single dose of 24 patients to a tumor to 24 patients. Clostridium novyi-NTranging 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.

The scientists were waiting 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 bacterium for one week, then antibiotics were administered to all 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 eliciting an immune response to 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, in which patients taking the pembrolizumab immunotherapy drug (Keytruda) will also be treated with a single injection of Clostridium novyi-NT, Said Janku. 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, Added Janku.

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.