title: 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.
authors: Department of Molecular Medicine, Chonnam National University, Gwangju 501-757, Republic of Korea.
authors: Sang Rok
authors: SR
authors: Lee
authors: Department of Surgery, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea.
authors: Young Kyu
authors: YK
authors: Park
authors: Deprtment of Microbiology, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea.
authors: Boo Ahn
authors: BA
authors: Shin
authors: Division of Liberal Arts & Teacher Training, Kwangju Women's University, Gwangju 506-713, Republic of Korea. Electronic address: hrpark@kwu.ac.kr.
authors: Hae-Ryoung
authors: HR
authors: Park
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D020382:Interleukin-18; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor
keywords: Cancer immunotherapy; Fusion protein; GM-CSF; GMIL-18; Tumor vaccine