61P - Unlocking the Power of Natural Killer Cells: Precision Selection with Cutting-Edge Microfluidics

Background

Natural killer (NK) cells may be particularly suited to cancer therapy. However, the heterogeneity of NK cell populations poses challenges in isolating highly functional subpopulations for therapeutic applications. This study presents a novel microfluidic platform that can select NK cells with enhanced avidity, aiming to improve the precision and efficacy of NK cell-based immunotherapies.

Methods

We used a microfluidics device that uses fluid shear stress to sort and isolate and sort NK cells based on their avidities to the target cells. Briefly, we sterilized our chip and coated it with fibronectin overnight and cultured lung cancer (A549) and ovarian cancer (SKOV3) cells for 24 hours until they achieved a monolayer. We then introduced NK cells on top of the monolayer and left these two types of cells to interact under static condition for 10 minutes. Using syringe pump, we applied fluid flow to induce shear ranging from 0.5Pa to 19.8 Pa in order to isolate the NK cells after each flow. To explore if avidity correlated with cytotoxicity, we cultured monolayer of A549 on our chip then introduced two types of NK cells: treated NK cells (adNK) and NK cells isolated from peripheral blood (cbNK). We followed the same protocol as described above to determine the NK cell type with high avidity.

Results

Our results show that at least 4.5 % and 4% cbNK cells remained attached to SKOV3 cells and A549 respectively after exposure to shear as high as 19.8 Pa. This avidity profile was different for adNK cells on A549. 30% of and NK cells remained attached to A549 cells after 19.8 Pa shear. This result also matched the cytotoxicity profile of adNK cells compared to that of cbNk cells for A549 cells.

Conclusions

In this study we used a novel method to sort and isolate NK cells based on their avidity to its target cancer cells. Although this device has been used to isolate and sort T cell population before, to our knowledge, for the first time we showed that NK cells can be isolated using their avidity to target cells. In addition, the higher avidity adNk cell aligned with its high cytotoxicity suggesting that selecting NK cells based on avidity may lead to selection of potent NK cells.

Legal entity responsible for the study

Imperial College London.

Funding

Imperial College London, Department of Bioengineering Imperial College London, Department of Life Sciences.

Disclosure

The author has declared no conflicts of interest.