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Technology: hIFN-y receptor antagonists


TIGO's technology platform is based on the modulation of human interferon gamma (hIFN-y) related effects.

Interferon gamma is species specific. hIFN-y is composed of 143 amino acids with a molecular weight of 17 kDa. The active form is a dimer.

The molecule exerts its effect via receptors located at the cellular surface of all cells with a cellular nucleus, i.e. in all cellls except red blood cells.

The primary cellular source of hIFN-y are Th1 cells and natural killer cells of the innate immune system.



IFN-y role in the human immune defense system
Source: Theofilopoulos et al. Arthritis Res 2001 3:136-141 doi:10.1186/ar290



Based on research by Prof. Ivanov and the late Prof. Tsanev from the Bulgarian Academy of Sciences, TIGO GmbH generates structures by manipulating the hIFN-y gene in such a way, that molecules result which competitively block the receptor of interferon gamma, thus reducing / preventing effects of hIFN-y.

These molecules carry the same number of amino acids as hIFN-y.

This
patented technology platform resulted in approximately 100 mutants.








Expression and Purification

Soluble hIFN-y mutants in high purity are available at laboratory scale, which are used in proof-of-concept assays.

Proof of Concept in Cellular Assay Systems


TIGO's hIFN-y receptor antagonists proved to inhibit the effect of a standard dose of hIGN-y in a kynurenine assay in Wish Cells by up to 30%. Such an incomplete inhibition is wanted in order to steer the therapeutioc effect without negative consequences to the immune system. Monoclonal antibodies to hIFN-y completely deprive the organism from circulating hIFN-y thus inducing considerable side effects.

Kynurenine Assay

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