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Scientific article
Open access
English

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

Published inNature Communications, vol. 8, 15327
Publication date2017
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.

Citation (ISO format)
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. doi: 10.1038/ncomms15327
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ISSN of the journal2041-1723
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Technical informations

Creation09/05/2017 3:52:00 PM
First validation09/05/2017 3:52:00 PM
Update time03/15/2023 2:14:33 AM
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