An immuno-therapy platform in development: StignumX

In mouse studies, Immunother Limited Company has prevented both breast cancer and autoimmunity (inflammatory bowel disease) with the same drug. That drug is called StignumX™.

StignumX™ has been validated to strengthen mammal immune systems. We are confident StignumX™ will prevent additional forms of cancer and additional autoimmune diseases.

 

How StignumX™ works:

Immunother Limited Company has found a way to combine the immune systems of three vertebrates to make one exceptionally strong immune system. Two of the immune systems can be the immune systems of two strains of mice that we can call A and B. When strain A is immunized with strain B tissue it makes anti-B plus anti-anti-A antibodies. The anti-B antibodies are called antigen-specific and the anti-anti-A antibodies are called antiidiotypic. Similarly, when strain B is immunized with strain A tissue it makes anti-A plus anti-anti-B antibodies. Again, the anti-B antibodies are called antigen-specific and the anti-anti-A antibodies are called antiidiotypic. In 1986 my lab at UBC reported that the immune response of A to B is complementary to (specific for) the immune response of B to A.

Response of A to B: anti-B plus anti-anti-A

Response of B to A: anti-A plus anti-anti-B

This relationship is called “second symmetry”, and is central to our technology.

In our experiments we treat a vertebrate C with a combination of anti-B plus anti-anti-B antibodies. The vertebrate C can be a third strain of mice or a person. The immune system is regulated by white blood cells called T cells. T cells have molecules on their surfaces called T cell receptors. In the context of clonal selection (check with your Immunology 101 course notes), the T cell receptors of a T cell define the specificity of the T cell. The anti-B antibodies stimulate anti-anti-B T cells and the anti-anti-B antibodies stimulate anti-B T cells. The V regions of the anti-anti-B T cells and the V regions of the anti-B T cells are specific for each other. Mutual selection (also known as co-selection) of the anti-anti-B T cells and the anti-B T cells takes the immune system of C to a new stable steady state in which the levels of anti-anti-B and anti-B white blood cells are elevated.

Our experiments show this is an exceptionally strong immune system. The technology is preventive. In an experiment with a transplantable breast tumor, the combination of antibodies was given at days -14 and -7 relative to transplant of the tumor. The growth of the tumor was reduced significantly, and the number of metastases to the lung was dramatically reduced. The two antibodies were needed, namely C3H anti-BL/6 plus BL/6 anti-anti-BL/6 to see the therapeutic effect.

We also obtained supporting cytokine data in this system. IL-1β and IL-6 were significantly down‑regulated, while TGFβ was significantly up‑regulated. IL‑1β and IL-6 are pro-inflammatory cytokines while TGFβ regulates inflammation. There was no change in the level of TNFα. Hence for three of the four cytokines there is a significant therapeutic effect resulting from the infusions of the antigen-specific plus antiidiotypic antibodies.

Essentially the same drug is effective in the prevention of inflammatory bowel disease. This time we used C3H anti-anti-C3H plus BL/6 anti-C3H antibodies, the converse of the antibodies used in the cancer experiment.

Recently we have obtained data that BL/6 anti-C3H plus C3H anti-anti-C3H is effective in the treatment of egg white allergy in a mouse model.

In conclusion, we see that a single type of two-component drug, namely antigen-specific plus antiidiotypic antibodies is effective in preventing breast cancer and preventing inflammatory bowel disease in mouse models.  Further, the same two-component drug is an effective treatment of egg white allergy in a mouse model.

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