dc.contributor.author
Kallert, Sandra M.
dc.contributor.author
Darbre, Stephanie
dc.contributor.author
Bonilla, Weldy V.
dc.contributor.author
Kreutzfeldt, Mario
dc.contributor.author
Page, Nicolas
dc.contributor.author
Mueller, Philipp
dc.contributor.author
Kreuzaler, Matthi
dc.contributor.author
Loehning, Max
dc.date.accessioned
2018-06-08T10:39:19Z
dc.date.available
2017-06-09T06:31:39.713Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20822
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24121
dc.description.abstract
Viral infections lead to alarmin release and elicit potent cytotoxic effector
T lymphocyte (CTLeff) responses. Conversely, the induction of protective
tumour-specific CTLeff and their recruitment into the tumour remain
challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV)
can be engineered to serve as a replication competent, stably-attenuated
immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to
dendritic cells for efficient CTL priming. Unlike replication-deficient
vectors, artLCMV targets also lymphoid tissue stroma cells expressing the
alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits
CTLeff responses of higher magnitude and functionality than those induced by
replication-deficient vectors. Superior anti-tumour efficacy of artLCMV
immunotherapy depends on interleukin-33 signalling, and a massive CTLeff
influx triggers an inflammatory conversion of the tumour microenvironment. Our
observations suggest that replicating viral delivery systems can release
alarmins for improved anti-tumour efficacy. These mechanistic insights may
outweigh safety concerns around replicating viral vectors in cancer
immunotherapy.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Live attenuated vaccines
dc.subject
Lymphocyte activation
dc.subject
Tumour vaccines
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Replicating viral vector platform exploits alarmin signals for potent CD8+ T
cell-mediated tumour immunotherapy
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Nature Communications. - 8 (2017), Artikel Nr. 15327
dcterms.bibliographicCitation.doi
10.1038/ncomms15327
dcterms.bibliographicCitation.url
http://www.nature.com/articles/ncomms15327
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000027155
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008298
dcterms.accessRights.openaire
open access