Interleukin-15 (IL-15) (IL-15)

Interleukin-15 (IL-15) is a pleiotropic cytokine essential for the development, survival, and activation of Natural Killer (NK) cells and memory CD8+ T cells (UniProt: P40933). In the context of EDIT-202, an iPSC-derived NK cell therapy developed by Editas Medicine, the IL-15 signaling axis is engineered to function in an autocrine and paracrine manner to enhance cell persistence and anti-tumor activity (Editas Medicine, 2022). This is achieved by the knock-in of a membrane-bound IL-15 (mbIL-15) or an IL-15/IL-15Rα fusion protein, which provides constitutive signaling through the IL-15 receptor complex (PubMed: 35413051). Furthermore, EDIT-202 incorporates a knockout of the CISH gene, which encodes a negative regulator of IL-15 signaling, thereby further boosting the metabolic fitness and cytotoxicity of the NK cells (PubMed: 32579482). This engineered axis allows the cells to remain active within the immunosuppressive tumor microenvironment without the systemic toxicity often associated with exogenous cytokine administration (PubMed: 33852854). By maintaining this signaling axis, EDIT-202 aims to overcome the limited lifespan and efficacy of conventional NK cell therapies in treating solid and hematologic malignancies.

Other names

IL-15Interleukin 15MGC9721IL15

The IL-15 signaling axis in EDIT-202 involves the expression of a membrane-bound IL-15/IL-15Rα fusion protein that activates the IL-2/IL-15 receptor beta (CD122) and common gamma chain (CD132) complex. This provides continuous, localized stimulation to the NK cells, enhancing their persistence and cytotoxicity without the need for exogenous IL-15 support (PubMed: 35413051, Editas Medicine).