Recombinant vaccinia virus expressing IL-2 generates effective anti-tumor responses in an orthotopic murine model of head and neck carcinoma

We evaluated the efficacy of a replication-competent, attenuated recombinant vaccinia virus (rvv) expressing IL-2 as a tumor vaccine in an immunocompetent murine model of head and neck squamous cell carcinoma. We implanted oral tumors by injection of tumor cells (SCC VII/SF) into the floor of the mouth of the syngeneic C3H/HeJ mice. Previous studies with this model suggested the presence of tumor-induced immune suppression. To circumvent the immune suppression we subcutaneously (s.c.) immunized the mice with irradiated, rvv-infected tumor cells prior to or along with intratumoral (i.t.) vaccination. A single s.c. vaccination invoked tumor-specific T cell proliferation and cytotoxicity. Mice treated by this protocol survived longer compared to those treated with i.t. vaccination alone. Tumor growth was significantly inhibited (P < 0.0002) and tumor regression was observed in all mice. The numbers of CD4(+) and CD8(+) lymphocytes as well as macrophages in the tumor beds and in tumor-draining lymph nodes were significantly increased in the mice treated by s.c. plus i.t. vaccination compared to s.c. or i.t. vaccination alone. These results suggested that s.c. vaccination along with i.t. vaccination increased antitumoral immunity and that CD4(+), CD8(+) lymphocytes as well as macrophages may play an important role in this antitumoral immunity.