Immune-mediated effector molecules can limit cancer growth, but lack of
sustained immune activation in the tumour microenvironment restricts
antitumour immunity. New therapeutic approaches that induce a strong and
prolonged immune activation would represent a major immunotherapeutic advance.
Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV)
and the clinically used Junin virus vaccine (Candid#1) preferentially
replicate in tumour cells in a variety of murine and human cancer models.
Viral replication leads to prolonged local immune activation, rapid regression
of localized and metastatic cancers, and long-term disease control.
Mechanistically, LCMV induces antitumour immunity, which depends on the
recruitment of interferon-producing Ly6C+ monocytes and additionally enhances
tumour-specific CD8+ T cells. In comparison with other clinically evaluated
oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising
antitumoural benefits. In conclusion, therapeutically administered arenavirus
replicates in cancer cells and induces tumour regression by enhancing local
immune responses
