dc.contributor.author
Grunewald, Laura
dc.contributor.author
Lam, Tobias
dc.contributor.author
Andersch, Lena
dc.contributor.author
Klaus, Anika
dc.contributor.author
Schwiebert, Silke
dc.contributor.author
Winkler, Annika
dc.contributor.author
Gauert, Anton
dc.contributor.author
Heeren-Hagemann, Anja I.
dc.contributor.author
Astrahantseff, Kathy
dc.contributor.author
Klironomos, Filippos
dc.contributor.author
Thomas, Alexander
dc.contributor.author
Deubzer, Hedwig E.
dc.contributor.author
Henssen, Anton G.
dc.contributor.author
Eggert, Angelika
dc.contributor.author
Schulte, Johannes H.
dc.contributor.author
Anders, Kathleen
dc.contributor.author
Kloke, Lutz
dc.contributor.author
Künkele, Annette
dc.date.accessioned
2021-10-04T14:40:03Z
dc.date.available
2021-10-04T14:40:03Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32176
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-31904
dc.description.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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
neuroblastoma
en
dc.subject
T cell infiltration
en
dc.subject
3D tumor model
en
dc.subject
bioprint technology
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
A Reproducible Bioprinted 3D Tumor Model Serves as a Preselection Tool for CAR T Cell Therapy Optimization
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
689697
dcterms.bibliographicCitation.doi
10.3389/fimmu.2021.689697
dcterms.bibliographicCitation.journaltitle
Frontiers in Immunology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
12
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34267756
dcterms.isPartOf.eissn
1664-3224