在确定的、无血清和无饲养层条件下从诱导多能干细胞分化 NK 细胞

Here the authors evaluated the potential of differentiating NK cells from centrally authenticated iPSCs under entirely chemically defined and serum-free conditions as well as their immunotherapeutic potential, after expansion in feeder-free media, against solid tumors targets. To address limitations of current differentiation approaches, the authors did not utilize feeder or stromal cell layers, TrypLE adaptation or peripheral blood during the differentiation process. The authors also evaluated the feasibility of utilizing centrally authenticated iPSC lines, thus circumventing protocol- and donor-induced variability associated with reprogramming approaches, and characterized these iPSC-NK cells in terms of cytotoxicity, cytokine production and degranulation potential against solid tumor cell lines and patient-derived targets.

Differentiation of iPSCs generated NK cells that were predominantly CD56 + /CD16 + /CD3 - and expressed NK activation markers NKG2D, NKp30, NKp44, NKp46 and DNAM-1. These iPSC-NK cells mediated effector functions, including cytotoxicity, degranulation and IFN-γ production, in response to solid tumor targets, including patient-derived cancer cells, and could be cryopreserved and expanded in culture.

The ability to produce NK cells under defined conditions and the functional responses elicited by these iPSC-NK cells suggest that they could represent promising effectors in clinical adoptive transfer settings as a renewable source of donor-independent NK cells for immunotherapy of solid tumors.