IL-23 as a therapeutic target
The Interleukin 23 (IL-23) cytokine is a heterodimeric cytokine consisting of the two subunits p19 and p40. It is an inducer of the Th17 cell population and a component of the IL-23/IL-17 immune pathway which is an orchestrator of many pathological conditions, including psoriasis.
Due to its crucial role in pathogenesis, the two IL-23 subunits are promising therapeutic targets for inflammatory conditions. The first approved biologic agent targeting IL-23 was ustekinumab (Stelara), a fully human monoclonal antibody against the shared IL-12/IL23 p40 subunit that was approved for the indication of psoriasis and Chron’s disease. Guselkumab (Tremfya), a monoclonal antibody targeting the IL23p19 subunit was recently approved for the treatment of psoriasis, while tildrakizumab (Ilumya), also targeting IL23p19, and other therapeutics are currently under development.
The humanized IL-23 mouse models
Two transgenic mice are currently under development, the TghIL23p19 mouse that expresses the human subunit of the Il23p19 and the TghIL23p40 that expresses the human subunit of the IL23p40. These mice are currently analyzed for spontaneous pathology development or tested with protocols of induced pathology to establish novel preclinical platforms that will allow the efficient evaluation of therapeutics targeting the inhibition of human IL23p19 and/or p40 subunits.