Natural killer (NK) cells are a key component of the innate immune system and are involved in early defense against viruses and cancer cells. NK cells have the ability to lyse cells without prior sensitization and therefore are the subject of intense interest to be potentially used as immunotherapeutic targets to treat cancer. The crucial element for using NK cells in immunotherapy is the ability to control the signaling and activation pathways. Recent work has shown that the cytokine-inducible SH2-containing protein (CIS), encoded by the Cish gene, can act as a checkpoint in NK activation by inhibiting IL-15 signaling, a major upregulator of NK cell activity. Furthermore, deletion of the Cish gene has been shown to increase the sensitivity of NK cells to IL-15, resulting in mice that are resistant to experimental metastasis.
Researchers at UC San Diego have developed a method whereby modified NK cells can be used to treat cancer. The modified NK cells exhibit hypersensitivity to cytokines, such as IL-2 and or IL-15 stimulation and maintain expansion and anti-tumor functions with lower concentrations of IL-2 and IL-15.
The inventors have developed human Cish-/- NK derived cells and methodology to use these cells for cancer therapy.
Compared to existing NK cell therapy, that uses unmodified NK cells, the inventors gene modified iPSC-derived Cish-/-NK cells have better anti-tumor effects. They also require lower doses of IL-2 and IL-15 to maintain expansion and anti-tumor function and can persist more than 3 weeks in vitro.
The technology is at the experimental stage with a large number of in vitro studies completed. The next phase of development is to start in vivo studies.
This technology is patent pending and available for licensing and/or research sponsorship.
Natural kill cells, NK cells, IL-2, IL-15, iPSC cells, immunotherapy, cancer therapy, Cish, modified immune cells, innate immunity, cytokine-inducible SH2-containing protein (CIS)