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

Kallert, Sandra M
Bonilla, Weldy V
Müller, Philipp
Kreuzaler, Matthias
Lu, Min
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Published in Nature Communications. 2017, vol. 8, p. 15327
Abstract 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.
PMID: 28548102
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Article (Published version) (1.2 MB) - public document Free access
Research group La Sclérose en plaques (908)
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KALLERT, Sandra M et al. Replicating viral vector platform exploits alarmin signals for potent CD8(+) T cell-mediated tumour immunotherapy. In: Nature Communications, 2017, vol. 8, p. 15327. https://archive-ouverte.unige.ch/unige:98397

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Deposited on : 2017-11-01

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