Cytokine-induced Expandable Memory NK Cells with Significant Metabolic, Epigenetic Remodeling, and Persistence Properties

This method can effectively and stably expand healthy donor-derived Peripheral NK (PBNK) cells by more than 200-fold within two weeks, with a purity exceeding 95%. Importantly, these ex vivo expanded NK (ExNK) cells exhibited hypomethylated state in the CNS-1 region (Conserved Noncoding Sequence 1) of IFNG gene, stronger metabolic ability, and enhanced effector function when compared to CIML NK cells. Based on these features, we named these expanded NK cells but still possess memory-like characteristics as mExNK (memory-like expanded NK cells).

Bulk mRNA-seq further firmly uncovered a high similarity between mExNK and CIML NK cells, with both highly expressing genes being related to proliferation, metabolism, and memory. Furthermore, we also test that these mExNK cells are superior much more than conventional expanded ExNK cells (cExNK). Taken together, the method described herein showed an enhanced expansion efficiency for human memory NK cells and would facilitate their clinic applications in cancer therapy.