dc.contributor.author
Ali, Solin
dc.contributor.author
Toews, Karin
dc.contributor.author
Schwiebert, Silke
dc.contributor.author
Klaus, Anika
dc.contributor.author
Winkler, Annika
dc.contributor.author
Grunewald, Laura
dc.contributor.author
Oevermann, Lena
dc.contributor.author
Deubzer, Hedwig E.
dc.contributor.author
Tüns, Alicia
dc.contributor.author
Jensen, Michael C.
dc.contributor.author
Henssen, Anton George
dc.contributor.author
Eggert, Angelika
dc.contributor.author
Schulte, Johannes Hubertus
dc.contributor.author
Schwich, Esther
dc.contributor.author
Rebmann, Vera
dc.contributor.author
Schramm, Alexander
dc.contributor.author
Künkele, Annette
dc.date.accessioned
2020-06-09T12:59:16Z
dc.date.available
2020-06-09T12:59:16Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/27398
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-27154
dc.description.abstract
Chimeric antigen receptor (CAR) T cell efficacy against solid tumors is currently limited by several immune escape mechanisms, which may include tumor-derived extracellular vesicles. Advanced neuroblastoma is an aggressive childhood tumor without curative treatment options for most relapsed patients today. We here evaluated the role of tumor-derived extracellular vesicles on the efficacy of CAR T cells targeting the neuroblastoma-specific antigen, CD171. For this purpose, CAR T cell activation, cytokine production, exhaustion, and tumor cell-directed cytotoxicity upon co-culture was evaluated. Tumor-derived extracellular vesicles isolated from SH-SY5Y neuroblastoma cells neither affected CAR T cell activation nor expression of inhibitory markers. Importantly, exposure of CD4+ CD171-specific CAR T cells to tumor-derived extracellular vesicles significantly impaired tumor cytotoxicity of CAR T cells. This effect was independent of neurotrophic receptor tyrosine kinases 1 or 2 (NTRK1, NTRK2) expression, which is known to impact immune responses against neuroblastoma. Our results demonstrate for the first time the impact of tumor-derived extracellular vesicles and non-cell-mediated tumor-suppressive effects on CD4+ CAR T cell efficacy in a preclinical setting. We conclude that these factors should be considered for any CAR T cell-based therapy to make CAR T cell therapy successful against solid tumors.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
immunotherapy
en
dc.subject
pediatric oncology
en
dc.subject
neuroblastoma
en
dc.subject
solid tumors
en
dc.subject
neurotrophic receptor tyrosine kinase
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Tumor-Derived Extracellular Vesicles Impair CD171-Specific CD4+ CAR T Cell Efficacy
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
531
dcterms.bibliographicCitation.doi
10.3389/fimmu.2020.00531
dcterms.bibliographicCitation.journaltitle
Frontiers in Immunology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media S.A.
dcterms.bibliographicCitation.volume
11
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
32296437
dcterms.isPartOf.eissn
1664-3224