Heat-inducible CAR-T overcomes adverse mechanical tumor microenvironment in a 3D bioprinted glioblastoma model

• DOI: 10.1016/j.mtbio.2024.101077
• Publication Date: 2024-05-03T02:46:32Z
• Authors: Min Tang; Yunjia Qu; Peixiang He; Emmie Yao; Tianze Guo; Di Yu; Nancy Zhang; Wisarut Kiratitan...; Yazhi Sun; Longwei Liu; Yingxiao Wang; Shaochen Chen
• Keywords: Matrigel; 3D bioprinting

Glioblastoma (GBM) presents a significant therapeutic challenge due to the limited efficacy of existing treatments. Chimeric antigen receptor (CAR) T-cell therapy offers promise, but its potential in solid tumors like GBM is undermined by physical barrier posed extracellular matrix (ECM). To address inadequacies traditional 2D cell culture, animal models, and Matrigel-based 3D culture mimicking mechanical characteristics tumor tissues, we employed biomaterials digital light processing-based bioprinting fabricate biomimetic models with finely tunable ECM stiffness independent composition. Our results demonstrated that increased material markedly impeded CAR-T penetration cytotoxicity models. The bioprinted enabled us examine influence on effectiveness, providing clinically pertinent evaluation tool for development stiff tumors. Furthermore, developed an innovative heat-inducible therapy, effectively overcoming challenges microenvironment.