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Intratumoral modulation of the

inducible co-stimulator ICOS by

recombinant oncolytic virus promotes

systemic anti-tumour immunity.

Zamarin D, Holmgaard RB, Ricca J, et al. Intratumoral modulation of the inducible co-stimulator
ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity.
Nature Communications 2017;8:14340.

ABSTRACT

Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour
immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that
intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression
of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the
tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL). In the bilateral flank tumour models, intratumoral
administration of NDV-ICOSL results in enhanced infiltration with activated T cells in both virus-injected and distant tumours, and
leads to effective rejection of both tumours when used in combination with systemic CTLA-4 blockade. These findings highlight that
intratumoral immunomodulation with an oncolytic virus expressing a rationally selected ligand can be an effective strategy to drive
systemic efficacy of immune checkpoint blockade.

https://www.ncbi.nlm.nih.gov/pubmed/28194010