Frontiers in Immunology (Jun 2021)
A Reproducible Bioprinted 3D Tumor Model Serves as a Preselection Tool for CAR T Cell Therapy Optimization
- Laura Grunewald,
- Laura Grunewald,
- Tobias Lam,
- Tobias Lam,
- Lena Andersch,
- Anika Klaus,
- Silke Schwiebert,
- Annika Winkler,
- Anton Gauert,
- Anja I. Heeren-Hagemann,
- Kathy Astrahantseff,
- Filippos Klironomos,
- Alexander Thomas,
- Alexander Thomas,
- Hedwig E. Deubzer,
- Hedwig E. Deubzer,
- Hedwig E. Deubzer,
- Hedwig E. Deubzer,
- Anton G. Henssen,
- Anton G. Henssen,
- Angelika Eggert,
- Angelika Eggert,
- Angelika Eggert,
- Angelika Eggert,
- Johannes H. Schulte,
- Johannes H. Schulte,
- Johannes H. Schulte,
- Kathleen Anders,
- Kathleen Anders,
- Lutz Kloke,
- Lutz Kloke,
- Annette Künkele,
- Annette Künkele,
- Annette Künkele,
- Annette Künkele
Affiliations
- Laura Grunewald
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Laura Grunewald
- Freie Universität Berlin, Berlin, Germany
- Tobias Lam
- Technische Universität Berlin, Berlin, Germany
- Tobias Lam
- Cellbricks GmbH Berlin, Berlin, Germany
- Lena Andersch
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Anika Klaus
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Silke Schwiebert
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Annika Winkler
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Anton Gauert
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Anja I. Heeren-Hagemann
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Kathy Astrahantseff
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Filippos Klironomos
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Alexander Thomas
- Technische Universität Berlin, Berlin, Germany
- Alexander Thomas
- Cellbricks GmbH Berlin, Berlin, Germany
- Hedwig E. Deubzer
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Hedwig E. Deubzer
- Neuroblastoma Research Group, Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany
- Hedwig E. Deubzer
- German Cancer Consortium (DKTK), Heidelberg, Germany
- Hedwig E. Deubzer
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Anton G. Henssen
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Anton G. Henssen
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- Angelika Eggert
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Angelika Eggert
- German Cancer Consortium (DKTK), Heidelberg, Germany
- Angelika Eggert
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Angelika Eggert
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- Johannes H. Schulte
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Johannes H. Schulte
- German Cancer Consortium (DKTK), Heidelberg, Germany
- Johannes H. Schulte
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Kathleen Anders
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Kathleen Anders
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Lutz Kloke
- Technische Universität Berlin, Berlin, Germany
- Lutz Kloke
- Cellbricks GmbH Berlin, Berlin, Germany
- Annette Künkele
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
- Annette Künkele
- German Cancer Consortium (DKTK), Heidelberg, Germany
- Annette Künkele
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Annette Künkele
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2021.689697
- Journal volume & issue
-
Vol. 12
Abstract
Chimeric antigen receptor (CAR) T cell performance against solid tumors in mouse models and clinical trials is often less effective than predicted by CAR construct selection in two-dimensional (2D) cocultures. Three-dimensional (3D) solid tumor architecture is likely to be crucial for CAR T cell efficacy. We used a three-dimensional (3D) bioprinting approach for large-scale generation of highly reproducible 3D human tumor models for the test case, neuroblastoma, and compared these to 2D cocultures for evaluation of CAR T cells targeting the L1 cell adhesion molecule, L1CAM. CAR T cells infiltrated the model, and both CAR T and tumor cells were viable for long-term experiments and could be isolated as single-cell suspensions for whole-cell assays quantifying CAR T cell activation, effector function and tumor cell cytotoxicity. L1CAM-specific CAR T cell activation by neuroblastoma cells was stronger in the 3D model than in 2D cocultures, but neuroblastoma cell lysis was lower. The bioprinted 3D neuroblastoma model is highly reproducible and allows detection and quantification of CAR T cell tumor infiltration, representing a superior in vitro analysis tool for preclinical CAR T cell characterization likely to better select CAR T cells for in vivo performance than 2D cocultures.
Keywords
