A 3D Bioprinted Breast Cancer Model for Immunotherapy

Despite substantial advancements in development of cancer treatments, lack of standardized and physiologically-relevant in vitro testing platforms limits the early screening of anticancer agents. A major barrier is the complex interplay between the tumor microenvironment and immune response. To tackle this, we developed a dynamic-flow based 3D bioprinted multi-scale vascularized breast tumor model, responding to chemo and immunotherapeutics. Heterotypic tumors were precisely bioprinted at pre-defined distances from a perfused vasculature, exhibited tumor angiogenesis and cancer cell invasion into the perfused vasculature. Bioprinted tumors treated with varying dosages of doxorubicin for 72 h portrayed a dose-dependent drug response behavior. More importantly, a cell based immune therapy approach was explored by perfusing HER2-targeting chimeric antigen receptor (CAR) modified CD8⁺ T cells for 24 or 72 h. Extensive CAR-T cell recruitment to the endothelium, substantial T cell activation and infiltration to the tumor site, resulted in up to ~70% reduction in tumor volumes. The presented platform paves the way for a robust, precisely fabricated and physiologically-relevant tumor model for future translation of anti-cancer therapies to personalized medicine.