Microphysiological vascularized solid tumor model for drugs and cell therapies screening

Abstract

Solid tumors present particular obstacles for cell therapies, which need to be reflected in pre-clinical models for effective therapy validation. For example, tumor biology varies along with the tumor mass, and the tumor microenvironment (TME), consisting of vasculature, stromal cells and immune cells, can become corrupted and promote resistance or prevent cell therapy targeting and efficacy. We developed an in vitro vascularized human solid tumor model which recapitulates these key features of the TME in a microfluidic device, allowing for more reliable and convenient drug and cell therapy validation. The model consists of a solid tumor spheroid surrounded by a perfusable vasculature, with a permeability value similar to in vivo physiology. We used the model to identify tumor-vasculature interactions, evaluate drug response, and evaluate cell therapy infiltration and cytotoxicity. By removing the cultured tumor microtissue from the device and performing spatial transcriptomics on standard paraffin-embedded sections, we identified known and novel genes involved in creating a pro-tumorigenic microenvironment.