Replicating viral vector platform exploits alarmin signals for potent CD8; +; T cell-mediated tumour immunotherapy

Kallert, Sandra M. and Darbre, Stephanie and Bonilla, Weldy V. and Kreutzfeldt, Mario and Page, Nicolas and Müller, Philipp and Kreuzaler, Matthias and Lu, Min and Favre, Stéphanie and Kreppel, Florian and Löhning, Max and Luther, Sanjiv A. and Zippelius, Alfred and Merkler, Doron and Pinschewer, Daniel D.. (2017) Replicating viral vector platform exploits alarmin signals for potent CD8; +; T cell-mediated tumour immunotherapy. Nature Communications, 8. p. 15327.

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Official URL: https://edoc.unibas.ch/76564/

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Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL; eff; ) responses. Conversely, the induction of protective tumour-specific CTL; eff; 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; eff; 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; eff; 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Aug 2020 11:27
Deposited On:20 Aug 2020 15:04

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