''Clostridium novyi''-NT is an attenuated form of ''
Clostridium novyi'' that is under investigation as a cancer treatment. It is one of several pathogenic species of ''
Clostridium
''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative ag ...
'' bacteria that have been examined for this purpose. The modification eliminated the secretion of
α-toxin.
[
]
Mechanism of action
Syngeneic
The word "syngenic" or "syngeneic" (from the Greek word for a relative) means genetically identical, or sufficiently identical and immunologically compatible as to allow for transplantation. For example, it may be used for something transplanted fr ...
and xenograft experimental tumors across multiple animal species were treated with injected or intravenous ''C. novyi''-NT spores, including colon and pancreatic cancer
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...
s in mice, aggressive squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
in rabbits, and glioblastomas in rats.
Effects included hemorrhagic necrosis, tumor cell lysis, and tumor regression. Intratumoral application increased spore concentrations in the tumor and reduced side effects. Bacteriolysis
One of the serum substances which is part of the dissolution process of bacteria, the enzymes will promote the dissolution of the bacterial cell wall and cause the death of the bacteria.
Bacteriolysin probably functions by deregulating lipoteic ...
in hypoxic tumor parts can be combined with chemotherapy and/or radiation that are more effective in proliferating, non-hypoxic areas at the cost of increased toxicity.
Normal cells are generally not hypoxic, preventing these bacteria from penetrating such tumors. Bacteria also potentially can stimulate the immune system, possibly offsetting the tumor-induced immunosuppression, such as from PD-L1.
''Clostridium novyi''
''C. novyi'' is ubiquitous in soil and feces and can infect mammals. Rare human infections can lead to gas gangrene are often fatal particularly after wounds or drug use. It secretes α-toxin.[
]
History
In 2014, researchers found that a modified strain of '' Clostridium novyi'' bacteria caused tumor shrinkage without damaging normal cells. Initial tests on mice were followed by tests on canines with naturally occurring cancers and on one human patient. The anaerobic bacteria stimulated an immune response at the site of the tumor destruction.
Of the sixteen dogs with soft-tissue sarcoma treated with the ''C. novyi''-NT therapeutic, three tumors disappeared for as long as two years, and another three reduced tumor size 30%. When the bacteria reached the edge of the tumor, they stopped killing cells around them due to the oxygen present in the environment of normal body tissue.myosarcoma
Myosarcoma is a malignant muscle tumor. People with myosarcoma often wake up with the feeling as if they had a cramp during their sleep.
Leiomyosarcoma is sarcoma of smooth muscle, and rhabdomyosarcoma is sarcoma of striated muscle
Striations me ...
within days. A phase 1 clinical trial (NCT01924689) began in 2014.[
]
See also
* '' Salmonella typhimurium''
* '' C. butyricum''
* '' C. tetani''
* '' C. histolyticum'' 17 and 18
* '' C. beijerinckii'' 19
* '' C. acetobutylicum''
* '' C. sporogenes'' ATCC13732
References
{{reflist, 30em
novyi-NT
Experimental cancer drugs