Anti-cancer efficacy of natural killer cells in breast cancer cell lines and patient-derived organoids

Background
Currently, immunotherapy through Adoptive Cell Transfer (ACT) of immune cells, such as T cells or Natural killer cells (NK cell), is being proposed as a new treatment in the treatment of various cancers. NK cell-based therapeutic research has been conducted mainly in blood cancer until recently and is currently being tried in many solid cancers.

Purpose
The purpose of the study is to examine the anti-cancer efficacy of natural NK cell-based ACT for breast cancer using breast cancer cell lines and patient-derived breast cancer organoids, which mighty be an alternative model to predict the outcome of developing therapeutics.

Methods

The isolated PBMCs from healthy donors were cultured and expanded following a previously published protocol. Characterization of NK cells was performed by flow cytometry and Enzyme-linked immunosorbent assay (ELISA). Expanded NK cells were evaluated for their anti-cancer efficacy in vitro (breast cancer cells MCF-7 and MDA-MB-453) and in vivo (xenograft breast cancer model using MCF-7 breast cancer cells). Breast cancer organoids using breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-453) and patient tissue were generated. Varying number of NK cells (1x10⁴ – 1x10⁵ cells) were applied to examine the cytotoxic effect of NK cells on the patient-derived organoids. The morphological and size changes of organoids were monitored for any sign of disintegration of the organoids for up to 2 weeks.

Results
In the 2 weeks expanded PBMCs, it was possible to secure a sufficient number of NK cells, and it was confirmed that NK cells had anti-cancer efficacy against breast cancer cell. In the xenograft animal model, the expanded NK cells tended to inhibit tumor growth, but they were not statistically significant.
The organoids derived from breast cancer cell lines and breast cancer patients were successfully cultured. In the MCF-7 xenografted tumor mass and organoids made of MCF-7 showed co-localized same ER and PR expression pattern.

However, in the case of breast cancer-derived organoids, the expression of receptors in the patient's original tumor and organoids was not completely consistent. In addition, no significant anticancer effects of NK cells have been confirmed in organoids derived from breast cancer patients.

Conclusion

NK cell-based treatment was judged to have value as an auxiliary treatment method rather than a main treatment method in the treatment of breast cancer. In the case of organoids derived from breast cancer patients, the expression patterns of receptors in the patient's original tumor and organoids did not completely match, which was thought to reflect the diversity and polymorphism of breast cancer cells. For more accurate characterization and evaluation of effectiveness as an alternative animal model, it will be necessary to conduct phenotypic analysis on a large number of organoids.

To be updated shortly..