Oncolytic virotherapy has garnered attention as an
antigen-agnostic therapeutic
cancer vaccine that induces
cancer-specific T cell responses without additional
antigen loading. As anticancer immune responses are compromised by a lack of antigenicity and chronic immunosuppressive microenvironments, an effective immuno-oncology modality that converts cold
tumors into hot
tumors is crucial. To evaluate the immune-activating characteristics of oncolytic vaccinia virus (VACV; JX-594, pexastimogene devacirepvec), diverse murine syngeneic
cancer models with different tissue types and immune microenvironments were used. Intratumorally administered mJX-594, a murine variant of JX-594, potently increased CD8+ T cells, including
antigen-specific
cancer CD8+ T cells, and decreased immunosuppressive cells irrespective of tissue type or therapeutic efficacy. Remodeling of
tumors into inflamed ones by mJX-594 led to a response to combined anti-PD-1 treatment, but not to mJX-594 or anti-PD-1 monotherapy. mJX-594 treatment increased
T cell factor 1-positive stem-like T cells among
cancer-specific CD8+ T cells, and anti-PD-1 combination treatment further increased proliferation of these cells, which was important for therapeutic efficacy. The presence of functional
cancer-specific CD8+ T cells in the spleen and bone marrow for an extended period, which proliferated upon encountering
cancer antigen-loaded splenic dendritic cells, further indicated that long-term durable anticancer immunity was elicited by oncolytic VACV.