Membrane-bound Interleukin-15 (mbIL15) with cytoDRiVE degron tag (mbIL15-cytoDRiVE)

The Degron-related domain tag on membrane-bound Interleukin-15 (mbIL15) is a synthetic regulatory component of the cytoDRiVE platform developed by Cytovia Therapeutics (Cytovia Therapeutics, 2023). This system utilizes a small-molecule-inducible degron tag fused to mbIL15 to provide precise control over cytokine signaling in engineered immune cells, such as CAR-NK or CAR-T cells (Cytovia Therapeutics, 2022). In its default state, the degron tag promotes the rapid proteasomal degradation of the mbIL15 protein, preventing its expression on the cell surface. When a specific cytoDRiVE small-molecule ligand is introduced, it binds to the degron domain, stabilizing the protein and allowing for its translocation to the plasma membrane (Business Wire, 2021). Once expressed, the mbIL15 provides essential survival and proliferation signals to the immune cells via autocrine and paracrine pathways, enhancing their anti-tumor activity (Liu et al., 2021). This technology is designed to overcome the limitations of systemic cytokine administration, which is often associated with severe toxicity and a short half-life (Waldmann, 2018). By restricting IL-15 activity to the engineered cells and controlling it with a drug, clinicians can potentially optimize the therapeutic window of cell-based immunotherapies.

Other names

cytoDRiVE-mbIL15Inducible membrane-bound IL-15Drug-regulated mbIL15mbIL15-degron construct

Small molecule-induced stabilization of a degron-tagged protein to control surface expression and signaling.