Cytokine-induced memory-like natural killer cell (CIML NK cell)

Cytokine-induced memory-like (CIML) natural killer (NK) cells are a specialized population of innate immune cells programmed through brief ex vivo exposure to a combination of cytokines—specifically interleukin-12 (IL-12), IL-15, and IL-18—to exhibit enhanced and sustained anti-tumor effector functions (Romee et al., 2016, Science Translational Medicine). This pre-activation induces stable epigenetic modifications that result in significantly increased production of interferon-gamma (IFN-γ) and enhanced cytotoxicity upon subsequent encounter with tumor cells or activating stimuli (Fehniger & Cooper, 2016, Trends in Immunology). Unlike standard NK cells, CIML NK cells possess a memory-like property, characterized by improved proliferation and long-term persistence in vivo, which can last for several weeks following infusion (Berrien-Elliott et al., 2022, Cancer Discovery). Clinically, CIML NK cell infusions are primarily utilized as an adoptive cell therapy for patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), where they have demonstrated the ability to induce complete remissions (Romee et al., 2016). The therapy is often supported by the administration of low-dose IL-2 or IL-15 superagonists (like N-803) to maintain cell viability and expansion in the patient (Bednarski et al., 2022, Blood). While generally safer than CAR-T cell therapies regarding the risk of severe cytokine release syndrome and neurotoxicity, challenges remain in optimizing their trafficking to solid tumors and overcoming the immunosuppressive tumor microenvironment.

Other names

Memory-like NK cellsIL-12/15/18-preactivated NK cellsCIML NK cell infusion

Adoptive transfer of ex vivo cytokine-preactivated NK cells that exhibit enhanced effector function and persistence to target and kill malignant cells.