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PD1-synNotch-IL-12 engineered NK cells is a preclinical-stage genetically engineered natural killer (NK) cell therapy. Developed by academic researchers at Golestan University of Medical Sciences, these NK cells (specifically NK-92 cells) are transduced with a lentiviral vector to express a chimeric PD1-synthetic Notch (synNotch) receptor. Upon binding to programmed death-ligand 1 (PD-L1) on tumor cells, the synNotch receptor is cleaved, releasing a transcriptional activator that drives the localized, target-dependent secretion of interleukin-12 (IL-12) and interferon-gamma (IFNγ). This localized cytokine release enhances the cytotoxic anti-tumor activity of the NK cells while minimizing systemic toxicity. The therapy has been investigated primarily for the treatment of PD-L1-positive breast cancers, including triple-negative breast cancer.
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