A New Approach Against Cancer, PD, and AD

iNtRON researches the relation between bacteriophages and human immunity, and iNtRON develops novel, first-in-class, biological drugs targeting cancers (colorectal cancer, CRC), neurodegenerative diseases (Parkinson’s disease and Alzheimer’s disease), and inflammatory diseases (Crohn’s Disease). Based on decades of experience and know-how accumulated in the field of bacteriophage and various platform technologies, iNtRON aims to expand the application of bacteriophage to the prevention and treatment of many different diseases utilizing the interaction with human immune system beyond bacteriophage’s ability to lyse bacteria.

Through this effort, we are working to analyze the correlation between bacteriophages and various immune systems in order to R&BD novel drug candidates in the immune-related disease.

iNtRON’s PHAGERIA® platform technology is being applied into animal and human fields. In the animal field, which is a pre-test market, iNtRON focuses on the development of antibiotic-alternatives based on potent and rapid antibacterial activity of bacteriophage in a specific bacterial strain as most countries are phasing-out conventional antibiotics with a broad spectrum killing many different bacterial strains at the same time. iNtRON has long been supplying antibiotic alternative products for animals in global.

Nevertheless, iNtRON’s primary focus of PHAGERIA® R&BD is the application in clinical uses for human. Based on the researches of the relationship between bacteriophage and the human immune system, iNtRON aims to develop novel bacteriophage-based drugs as an effective treatment for intractable diseases (cancers and brain diseases). iNtRON will achieve it by using bacteriophage’s ability to control the human microbiota environment and eventually regulate the immune system in human so it could be turned on / off wanted or unwanted immune system the way it is helpful.

Effect of Bacteriophage Dynamics on Human Health and Growth

The dynamic cycle of bacteriophage can be divided into two categories as follows:
• Lytic cycle : The lytic cycle results in the destruction of the infected cell and membrane of bacteria. In the lytic cycle which is also referred to as the "reproductive cycle", the phage attaches itself to the surface of the host cell in order to inject its DNA into the cell and replicates. The newly formed progeny phages are released from the infected cell by lysis the host cells.
• Lysogenic cycle : Unlike lytic phages, lysogenic phages do not lyse the host cell straight away after infection. Instead, after lysogenic phages insert their DNA into bacterial cells, the phage DNA first integrates into the bacterial chromosome to produce the prophage. When the bacterium reproduces, the prophage is also copied and is present in each of the copied cells. The copied cells can continue to replicate with the prophage present or the prophage can be converted to lytic phages by exiting from the bacterial chromosome to initiate the lytic cycle. Bacteriophage dynamics in the human gut vary with age, diet and lifestyle; therefore, it is important to maintain a healthy bacteriophage environments or phageome in our gut.

Gut Microbiome

To understand how changes in the gut microbiota by bacteriophages affect the host immune response, we need to understand the interaction between the gut bacteria and the immune system. Researchers have consistently reported that the microbiome is closely related to cell development and regulation of immune responses. In general, immune cells in humans and animals become activated (lymphoid follicle development, IgA secretion, CD4+T and NK cell maturation) and acquire defensive power against foreign microbes upon exposure. It helps the immune cells to maintain homeostasis.

Some Clostridia species play an important role in regulating anti-inflammation immune response that induces mucosal regulatory T cells (Treg) accumulation and IL-10 production. This interaction has been also reported to correlate with the formation of short chain fatty acids (SCFAs) produced by microbial fermentation of fibers. In addition, gut bacterial populations have been reported to play an important role in preventing colonization and metastasis of pathogenic bacteria. Recent research has been reporting that phage-mediated changes in the gut microbiota can influence immune signaling. In order to maintain healthy gut microbiome or phageome, it is important to apply bacteriophage-mediated bacterial dissolution mechanisms to certain harmful bacteria to induce pathogen-associated molecular patterns (PAMP) to be released, resulting good balances in overall gut microbiome or phageome.

The R&BD Expansion of PHAGERIA®

  1. 01Anti-cancer
    • Colorectal cancer (CRC)
    Bacteriophages can be used for the purpose of targeting bacteria affecting the occurrence and progression of cancer indirectly. Moreover, bacteriophages also can be used as a cancer treatment directly by displaying cancer-associated antigens (CAA) on the capsid surface of bacteriophages.
  2. 02Inflammatory diseases
    • Crohn’s disease (CD)
    Specific bacteriophages have properties to down-regulate the human immune response. By using the property, bacteriophages can be used for the treatment of inflammation.
  3. 03Neurodegenerative diseases
    • Parkinson’s disease
    • Alzheimer’s disease
    Bacteriophage can be used to target the bacteria related to the occurrence and progression of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In addition, bacteriophages can be utilized to treat neurodegenerative diseases by inhibiting the aggregation of virulence factors such as alpha-synuclein in the body.