Effects of tumor vaccine expressing Granulocyte-Macrophage Colony Stimulating Factor and interleukin-18 fusion on cancer cells and its possible application for cancer immunotherapy

Abstract

To access antitumor effects of a combined Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and interleukin-18 (IL-18), cDNA fusion of murine GM-CSF and mature IL-18 (GMIL-18) was constructed and transfected in mammalian cells. GMIL-18 fusion protein was highly secreted and displayed bifunctional activities, possessing immune response initiation and cytokine roles, including IFN-γ induction in mouse splenocytes and increased proliferation of GM-CSF-dependent cells, M-NSF-60. The GMIL-18 secreting tumor vaccine was generated and it strongly stimulated differentiation of dendrite cells (DCs) and effusive CD8⁺ and CD4⁺ cell infiltration into tumor mice. Moreover, growth of CT26 mouse colon cancer cells was significantly retarded by GMIL-18 (CT26GMIL-18), but not by CT26GM-CSF- or CT26IL-18. The efficiency of prophylactic vaccination was greater than that of therapeutic vaccination in terms of tumor size and its inhibitory role in proliferation. In micrometastasis analysis of tumor models, γ-ray irradiated GMIL-18 tumor vaccine showed a smaller number of liver-meta tumor nodules in mouse liver cells. We concluded that bifunctional GMIL-18 fusion protein could be applied as an immune therapy for cancer treatments.

Keywords: Cancer immunotherapy; Fusion protein; GM-CSF; GMIL-18; Tumor vaccine.