NK-92 cells retain vitality and functionality when grown in standard cell culture conditions

Abstract

NK-92 cells are an off-the-shelf, cell-based immunotherapy currently in clinical trials for a variety of cancer types. As the most ‘NK-like’ cell line available, it is also an important research tool. To date, NK-92 cells have been cultivated in a costly and time-consumingly prepared specialized medium, complicating research with these cells. Here we show that NK-92 cells grow in the comparatively user-friendly RPMI medium supplemented with IL-2. We demonstrate that their metabolic activity and replication rates are even improved in RPMI. Furthermore, they can be grown in cell culture dishes and do not need to be expanded in ventilated flasks. We show that in RPMI the cells retain functional characteristics relating to receptor expression, IFN-γ secretion, and killing. Our findings will enable more researchers to work with and manipulate this cell line, hopefully leading to further discoveries and improved therapies.

Advances in natural killer cell therapies for breast cancer

“…NK-92 cells are an enticing substitute for endogenous NK cells because of their high cytotoxicity against tumor cells, which they probably owe to a lack of MHCresponsive inhibitory receptors. 143 Anti-ErbB2 CAR NK-92 cells are cytolytic for ErbB2-expressing BC cells without prior sensitization, and their function and receptor expression are not affected by CAR expression. These cells suppress BC cells' growth in vivo as well as reducing lung metastasis and increasing IFNc secretion.…”

“…Their anticancer activity could be further enhanced as well. 173 Kotzur et al 143 showed that it is possible to produce NK-92 cells quicker, cheaper and easier while still maintaining their ability to cause cytotoxicity. This makes them even easier to use and supports the therapeutic and research utility of these cells.…”

“…The BC preclinical studies that followed used either PB 137,139 or NK‐92 cell lines 140–142 as a source. NK‐92 cells are an enticing substitute for endogenous NK cells because of their high cytotoxicity against tumor cells, which they probably owe to a lack of MHC‐responsive inhibitory receptors 143 . Anti‐ErbB2 CAR NK‐92 cells are cytolytic for ErbB2‐expressing BC cells without prior sensitization, and their function and receptor expression are not affected by CAR expression.…”

Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond

“…The benefits of using NK-92-based cellular therapies are manyfold. It possesses excellent cytotoxic function related to its overexpression of several activating receptors, down-regulation of inhibitory receptors, and high expression of lytic granules [73]. Moreover, the cell line is highly proliferative, easily acquired, and importantly, homogeneous in phenotype, allowing for a consistent and reproducible platform for translation of advanced cellular therapies [74].…”

“…Due to their derivation from an NK cell neoplasm, NK-92 cells must be irradiated to prevent malignant proliferation, thus limiting their capacity for in vivo expansion and persistence [77]. Other limitations of NK-92 cells include a susceptibility to targeting by host NK cells, high dependence on exogenous IL-2 for survival, and the absence of CD16 [73,78]. To this end, high-affinity NK cells (haNKs) have been developed by engineering NK-92 cells to endogenously express IL-2 along with high-affinity CD16 receptors carrying the 158V polymorphism, allowing for potent ADCC function [79].…”