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

Min Tang; Yunjia Qu; Peixiang He; Emmie Yao; Tianze Guo; Di Yu; Nancy Zhang; Wisarut Kiratitanaporn; Yazhi Sun; Longwei Liu; Yingxiao Wang; Shaochen Chen

Materials Today Bio (Jun 2024)

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

Min Tang,
Yunjia Qu,
Peixiang He,
Emmie Yao,
Tianze Guo,
Di Yu,
Nancy Zhang,
Wisarut Kiratitanaporn,
Yazhi Sun,
Longwei Liu,
Yingxiao Wang,
Shaochen Chen

Affiliations

Min Tang: Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
Yunjia Qu: Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Peixiang He: Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Emmie Yao: Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
Tianze Guo: Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093, USA
Di Yu: Department of Human Biology, University of California San Diego, La Jolla, CA, 92093, USA
Nancy Zhang: Department of Human Biology, University of California San Diego, La Jolla, CA, 92093, USA
Wisarut Kiratitanaporn: Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA
Yazhi Sun: Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
Longwei Liu: Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA; Corresponding author.
Yingxiao Wang: Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA; Corresponding author.
Shaochen Chen: Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093, USA; Corresponding author. Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA

Journal volume & issue: Vol. 26
p. 101077

Abstract

Read online

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

Published in Materials Today Bio

ISSN: 2590-0064 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.journals.elsevier.com/materials-today-bio

About the journal

Abstract

Keywords