Ex Vivo Natural Killer Cell Assay Using 3D Bioprinted Cervical Cancer Tumor Models

Presenting a more efficient natural killer cell assay for immuno-oncology research. Automated workflow with the BIO X 3D bioprinter, droplet-based bioprinting and co-culturing.​

The naturally occurring immune cells, dubbed natural killer (NK) cells, are a type of white blood cell. More specifically, NK cells are equipped with enzymes that can target and kill cancerous cells. To better study this immuno-oncology response and identify factors that influence its efficacy, we bioprinted cervical cancer tumor model. To do so, we used the droplet printing function on the BIO X 3D bioprinter and dispensed human cervical cancer cells SiHa and CaSki within a collagen I matrix into a 96-well microplate. Subsequently, we co-cultured the cancer cells with human peripheral blood-derived NK cells. Upon further analysis with bright-field imaging, we observed a decrease in tumor cell viability in the presence of higher concentrations of NK cells. This dip in viability confirms the concentration-dependent killing efficacy of natural killer cells. 

In summary, this protocol leverages the versatility of the BIO X, including droplet-based bioprinting. As an optimized workflow, it could accelerate drug screening and the clinical translation of personalized therapies. Finally, this cell assay is scalable, compatible with high-throughput imaging analysis, and translatable to other tumor models. 

Learn how:

  • Droplet 3D bioprinting is an automated process to reproducibly fabricate tumors with human cervical cancer cells SiHa and CaSki. 
  • These droplet tumoroids are a versatile in vivo-like model to facilitate immuno-oncology investigations. 
  • Remaining confined within the collagen matrix kept the bioprinted cancer cells viable for the duration of co-culture study with NK cells. 
  • A higher concentration of NK cells led to an increase in cancer cell killing. 
  • This NK cell cancer-killing assay is compatible with high-throughput imaging workflows for downstream analysis. 
  • This protocol can be adapted to other tumors to accelerate drug screening and the clinical translation of personalized therapies. 

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