Preclinical CAR T-Cell Testing: Evaluating Efficacy and Toxicity in a 3D Perfused Melanoma Model

Abstract 

Preclinical models such as cancer-on-a-chip systems are at the forefront of cancer research; however, preclinical CAR T-cell testing models that capture the full immunological cascade of these immunotherapies remain scarce.

These processes include circulation in the blood stream, transendothelial migration, tumor infiltration, and cytolysis of cancer cells. Recreating the physical and biochemical barriers imposed by the tumor microenvironment using advanced in vitro systems is critical for investigating CAR T cell performance against primary tumors, while simultaneously providing insights into potential adverse effects. 

As part of Melomanes, an EU-wide research consortium dedicated to the development of an immunotherapy combining anti-HLA-G CAR T cells and magnetic nanoparticles capable of inducing localised hyperthermia, this project aims to develop an advanced melanoma-on-a-chip system to evaluate the therapeutic efficacy and safety of CAR T cells. This model is developed using the PhysioMimix® Core platform (CN Bio Innovations), enabling medium circulation to model blood flow. A Transwell®-based dual-compartment strategy enables chemokine-controlled immune cell migration across a monolayer of human umbilical vein endothelial cells (HUVECs). Such human-based preclinical models offer a pathway to improved predictive accuracy while reducing the reliance on in vivo studies.