A new immunocompetent OOC platform for modeling the 3D tumor microenvironment with capillary flow-driven immune cells

One of the most unmet challenges of microphysiological systems (MPS) is related to more predictive and fully humanized in vitro models for immune-oncology. The preclinical assessment of immunotherapies is currently carried out through 2D cell culture in static conditions, and in vivo xenografts or genetically engineered animal models, generated by the engraftment of PDXs into immunodeficient mice bearing human immune cells, but cost, time, and complete immune-compatibility remain important challenges.
A novel Multi-In Vitro Organ (MIVO) organ on a chip (OOC) platform has been recently developed to culture immunocompetent tumor models, with circulating immune cells under proper physiological culture conditions.
Biologically-relevant cancer samples (up to 5 mm) or patient biopsies are cultured within the MIVO chamber, while human immune cells (e.g. Natural Killer cells, NK) are able to (i) circulate in the OOC mimicking the blood capillary flow, (ii) extravasate through a permeable barrier resembling the vascular barrier, (iii) infiltrate the cancer tissue.
A human 3D neuroblastoma model with proper immuno-phenotype was optimized to develop a complex tumor/immune cell coculture as a paradigm of an immune-oncology screening platform (Marrella A et al, 2019). NK cells have been introduced within the capillary fluid flow circulation of the MPS and their migration and infiltration towards the 3D tumor model was analyzed. Preliminary flow cytometry analysis highlighted that tumor cell viability seems to be reduced in the embedded co-culture of tumor and NK cells, suggesting an effective anti-tumor NK cell-mediated activity. Importantly, a tumor-specific NK cell extravasation was observed, with DNAM1+ NK cells infiltrated within 3D tumor models.
In conclusion, we generated a functional and relevant human model, through the adoption of OOC device, that can be efficiently employed as an immune-oncology screening platform, both for pharmacological treatments and for cell-based therapies, that could be “infused” into the platform for testing their journey and activity toward tumor cells.