Replicating viral vector platform exploits alarmin signals for potent CD8<sup>+</sup> T cell-mediated tumour immunotherapy.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_917BF046248A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Replicating viral vector platform exploits alarmin signals for potent CD8<sup>+</sup> T cell-mediated tumour immunotherapy.
Journal
Nature communications
Author(s)
Kallert S.M., Darbre S., Bonilla W.V., Kreutzfeldt M., Page N., Müller P., Kreuzaler M., Lu M., Favre S., Kreppel F., Löhning M., Luther S.A., Zippelius A., Merkler D., Pinschewer D.D.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
26/05/2017
Peer-reviewed
Oui
Volume
8
Pages
15327
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL <sup>eff</sup> ) responses. Conversely, the induction of protective tumour-specific CTL <sup>eff</sup> 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 CTL <sup>eff</sup> 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 CTL <sup>eff</sup> 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.
Keywords
Alarmins/immunology, Animals, Antigens, Neoplasm/immunology, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, Cell Line, Tumor, Dendritic Cells/immunology, Gene Expression Profiling, Genetic Engineering, Genetic Vectors/genetics, Genetic Vectors/immunology, Genetic Vectors/therapeutic use, HEK293 Cells, Humans, Immunotherapy/methods, Interleukin-33/genetics, Interleukin-33/immunology, Lymphocyte Activation/immunology, Lymphocytic choriomeningitis virus/genetics, Mesocricetus, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Neoplasms/immunology, Neoplasms/therapy, T-Lymphocytes, Cytotoxic/immunology, Tumor Microenvironment/immunology, Vaccines, Live, Unattenuated/immunology, Virus Replication/genetics, Virus Replication/immunology, Xenograft Model Antitumor Assays
Pubmed
Web of science
Open Access
Yes
Create date
06/06/2017 20:46
Last modification date
20/08/2019 15:54
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