Clostridium novyi-NT as Next Generation Probiotics

Live biotherapeutic products (LBPs), also termed as next-generation probiotics (NGPs), are rapidly developing because of their therapeutic potential. Clostridium organisms have promising potential in the development of cancer therapy. Creative Biolabs is committed to the research and development of novel NGPs, including Clostridium organisms. We aim to usher in an era of broader use of Clostridium organisms as biotechnological therapy. Our experienced experts in microecological innovative drug development can help you get milestone success in the NGPs project.

Introduction of Clostridium novyi-NT

Micrographs of C.novyi spores and outgrowth.Fig.1 Micrographs of C.novyi spores
and outgrowth. (Staedtke, 2016)

Clostridium novyi-NT (C.novyi) is a highly active bacterium that is very sensitive to oxygen. Bacterial spores can only germinate under low oxygen conditions. It is ubiquitous in soil and feces and can infect mammals. Rare human infections can cause gas gangrene that is often fatal particularly after wounds or drug use. With the increasing study of gut microbiota and its constituent actors, novel therapeutics based on LBPs has appeared that particularly given the phylogenetic range and relatively unknown characteristics of the live organisms under investigation. C.novyi is currently under investigation as a promising candidate for cancer treatment.

Clostridium novyi-NT for Cancer Therapy

Therapeutic interventions usually focus on the well-vascularized outer shell of the tumor rather than targeting the internal hypoxic core, which makes up an important part of the tumor's mass. To this end, we studied the potential of using live anaerobic bacteria to destroy the tumor core. The best cancer treatment strategy is to target tumor cells without harming normal healthy cells. Directed enzyme prodrug therapy (DEPT), using the specific enzymes called Prodrug Converting Enzymes (PCEs), which can convert from non-functional form to highly-toxic form near the tumor that only damages cancer cells.

Depiction of Clostridial-Directed Enzyme Prodrug Therapy (CDEPT). Fig.2 Depiction of Clostridial-directed enzyme prodrug therapy (CDEPT). (Kubiak, 2015)

The ability of C.inovyi to tumors with hypoxia has been observed in nearly all solid cancers. Once administered, C.novyi spores germinate locally within tumors and accurately spread throughout the tumor and its microsatellites, which may lead to hemorrhagic necrosis, tumor cell lysis and tumor regression. C.novyi has endured pre-clinical efficacy and toxicity assessments in several animal models. It has been reported that C.novyi spores delivered to mice by a single intravenous dose lead to substantial tumor regressions in most animal models. It also showed excellent tumor colonizing properties in the preclinical setting.

Among the sixteen dogs with soft-tissue sarcoma, after treatment with C.novyi, three tumors disappeared in two years, and the size of another three tumors reduced 30%. When the bacteria reach the edge of the tumor, they stop killing cells around them because of the oxygen present in the environment of normal body tissue.

Histological sections of rodent glioblastomas during C.novyi treatment. Fig.3 Histological sections of rodent glioblastomas during C.novyi treatment. (Staedtke, 2016)

Mechanism of Action

C.novyi can induce a strong inflammatory response involving pro-inflammatory cytokines such as IL-6, G-CSF, MIP-2, and TIMP-1 that recruit a large number of immune cells to the infection site to produce a durable adaptive anti-tumor immunity. C.novyi is expected to become a cancer treatment agent. Pre-clinical and early human experiences proved the potential of C.novyi in cancer treatment.

Our Services

  • Experimental design to meet specific demands
  • Screening and isolating potential NGPs
  • Identification and characterization of novel and disease-specific NGPs
  • Biological safety tests, such as growth dynamics, antibiotics sensitivity pattern tests, etc.
  • cGMP manufacturing with different scales

Creative Biolabs focuses on the clarification of the mechanism of action of NGPs and their development to accelerate their clinical applications. If you have any scientific research requirements or questions, please feel free to contact us.

References

  1. Kubiak, Aleksandra. M.; Minton, Nigel. P. The potential of clostridial spores as therapeutic delivery vehicles in tumor therapy. Res. Microbiol. 2015, 166:244-54.
  2. Staedtke, V.; et al. Clostridium novyi-NT in cancer therapy. Genes & Diseases. 2016, 144-152.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

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