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transforming growth factor-beta-imprinted natural killer cells

Development stage: Phase 2
Lead developer: Nationwide Children’s Hospital and Ohio State University Comprehensive Cancer Center
Modality: CAR-NK Cells → Other Engineered Cells → Adoptive Cell Transfer → Cell Therapies, Lymphokine-Activated Killer Cells → Native Immune Cells → Adoptive Cell Transfer → Cell Therapies
Administration: Intravenous

Overview

Transforming growth factor-beta-imprinted natural killer cells (TGFβi NK cells) are a type of modified Natural Killer (NK) cell designed to overcome the immunosuppressive effects of Transforming Growth Factor-beta (TGF-β) within the tumor microenvironment. TGF-β is a potent immunosuppressive cytokine that typically inhibits the anti-tumor responses of NK cells. However, by activating and expanding NK cells in the presence of TGF-β, these cells undergo an "imprinting" process. This imprinting leads to a phenotype characterized by hypersecretion of pro-inflammatory cytokines, such as interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα), and altered cytotoxicity against tumor targets. Crucially, TGFβi NK cells exhibit decreased sensitivity to TGF-β-mediated suppression, a resistance that persists even after the removal of TGF-β. The mechanism involves a marked suppression of SMAD3 and T-bet, associated with altered chromatin accessibility, which contributes to their enhanced anti-tumor function. These modified NK cells hold potential as a cell-based immunotherapy for various cancers.

Other names: TGF-beta-imprinted natural killer cells

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