Swiss scientists have created artificial viruses that can be used to target cancer. These designer viruses alert the immune system and cause it to send killer cells to help fight the tumor. The results provide a basis for innovative cancer treatments.
2017 Study 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.
- Designer Viruses Stimulate the Immune System to Fight Cancer, University of Basel, 26 May 2017.
- Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy, Nature Communications, doi:10.1038/ncomms15327, 26 May 2017.
- Image : Stable transgene expression and attenuation of artLCMV in vivo, nature, Figure 2, 26 May 2017.