18 August 2014

Genetically modified bacteria destroy tumors

Johns Hopkins University researchers have shown that a modified version of the bacteria Clostridium novyi (C. novyi-NT) created by them has a strong and highly specific antitumor effect when administered to mice, dogs and humans.

In pictures from the site hopkinsmedicine.org on the left – Gram staining of C.novyi-NT bacteria multiplying in the dog's tumor. In the image, the bacteria are dark sticks. On the right is the staining of the dog's tumor with hematoxylin and eosin after therapy with C.novyi-NT. Light pink areas are necrosis zones adjacent to the zones of viable tumor cells. Black inclusions are calcified fragments of tissue.The natural form of C.novyi occurs in soil and in some cases can cause tissue-damaging infection in cattle, sheep and humans.

These bacteria actively multiply only in oxygen-depleted conditions, which makes them a potential means of combating oxygen-deprived cells inside tumors that are poorly treatable using traditional methods of chemo- and radiotherapy. To increase the safety of such therapy, the researchers removed one of the genes encoding toxins from the clostridium genome.

As part of the study, modified clostridium spores were injected directly into the tumor area to 16 domestic dogs (tumors arose naturally). 21 days after the first administration of bacterial spores, positive treatment results were registered in 6 animals. In three of them, the tumor was completely destroyed, and in the remaining three, the largest diameter of the tumor decreased by at least 30%.

At the same time, most dogs had side effects characteristic of bacterial infections: fever, abscess in the tumor area and inflammation.

During a phase I clinical trial, a patient with a late-stage soft tissue tumor of the abdominal cavity was injected with modified clostridium spores directly into a metastatic tumor of the arm. This led to a significant reduction of the tumor both around and inside the bone and was accompanied by a strong inflammatory reaction and the formation of an abscess.

According to the authors, the clinical trial is currently ongoing, but its results are not yet available. They expect that the severity of the patients' response to treatment will vary significantly.

The researchers also note that therapy with modified clostridium can be combined with traditional methods of chemo- and radiotherapy. The effectiveness of such combinations is already being studied in experiments on mice.

The results of an earlier series of experiments on mice showed that infection of the tumor with clostridium can induce a powerful antitumor immune response that ensures the destruction of metastases for a long time after the end of therapy. However, these results still need to be replicated in animal models and in clinical trials.

Article by N.J. Roberts et al. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses is published in the journal Science Translational Medicine.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Johns Hopkins University School of Medicine:
Injected Bacteria Shrink Tumors in Rats, Dogs and Humans

18.08.2014

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