MIVO^®-Based Immune-on-Chip to Recapitulate NK Cell Infiltration and Cytotoxicity Against 3D Cancer Models

This application note shows a novel tumor–immune organ-on-chip model developed on the MIVO® platform. The study recapitulates NK cell migration, infiltration, and activation against neuroblastoma cells under physiological fluid flow, offering a predictive tool for immuno-oncology screening.

The development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. A tumor–immune organ-on-chip model was established for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D neuroblastoma (NB) matrix, and activation against NB cancer cells in a humanized, fluid-dynamic environment.
The NB cancer model was developed using HTLA-230 cells encapsulated in 3D FlowGel and cultured within the MIVO® platform under dynamic flow conditions, while NK cells were introduced in circulation. This setup was used to create an immune-competent environment and analyse immune cell extravasation and functional infiltration into the tumor matrix. Cell viability and expression were assessed through fluorescence imaging, immunostaining and flow cytometry.
Results show that circulating NK cells actively initiate a spontaneous “extravasation” process toward the tumor niche, displaying their cytotoxic effect against tumor cells. By combining FlowGel-based 3D culture with the dynamic perfusion capabilities of the MIVO® system, we established a physiologically relevant immune-on-chip model to assess immune cell behaviour and tumor response.