Chemotherapeutics and CAR-T Cell-Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model

摘要

Despite substantial advancements in development of cancer treatments,lack of standardized and physiologically-relevant in vitro testing platformslimit the early screening of anticancer agents. A major barrier is the complexinterplay between the tumor microenvironment and immune response.To tackle this, a dynamic-flow based 3D bioprinted multi-scale vascularizedbreast tumor model, responding to chemo and immunotherapeuticsis developed. Heterotypic tumors are precisely bioprinted at pre-defineddistances from a perfused vasculature, exhibit tumor angiogenesis andcancer cell invasion into the perfused vasculature. Bioprinted tumors treatedwith varying dosages of doxorubicin for 72 h portray a dose-dependent drugresponse behavior. More importantly, a cell based immune therapy approachis explored by perfusing HER2-targeting chimeric antigen receptor (CAR)modified CD8+ T cells for 24 or 72 h. Extensive CAR-T cell recruitment to theendothelium, substantial T cell activation and infiltration to the tumor site,resulted in up to ≈70% reduction in tumor volumes. The presented platformpaves the way for a robust, precisely fabricated, and physiologically-relevanttumor model for future translation of anti-cancer therapies to personalizedmedicine.