title: A novel chimeric DNA vaccine: enhancement of preventive and therapeutic efficacy of DNA vaccine by fusion of Mucin 1 to a heat shock protein 70 gene.
abstract: Intensive efforts to improve vaccines against cancer are currently outgoing. Mucin 1 (Muc1) is a tumor-specific antigen that is overexpressed and heavily glycosylated in a variety of adenocarcinomas. In the present study, the efficacy of an anticancer DNA vaccination strategy was demonstrated using Muc1 fusion vaccines. To enhance antigen presentation and tumor-suppressive efficacy, a chimeric Muc1 vaccine was designed, encoding the transmembrane- and C-terminal domain-deleted Muc1 gene (∆TM) fused to the human HSP70 gene. To confirm the expression and secretion of fusion protein, cell culture supernatants were subjected to Western blotting. We found secreted Muc1 ΔTM-HSP0 fusion protein in the supernatants. These results demonstrate that the Muc1 ΔTM-HSP0 construct can be efficiently expressed and secreted from transfected cells. When the chimeric Muc1 vaccine was administered to mice, antigen-specific cellular immune responses were observed. Notably, we observed that antigen-specific lymphocyte proliferation and cytotoxic responses were effectively induced only in the group of mice that had been vaccinated with the chimeric Muc1 vaccine. Concurrent with the Muc1-specific tumor-suppressive effect, the growth of established Muc1-expressing B16 mouse melanoma cells was also significantly inhibited by vaccination with the chimeric Muc1 vaccine. The growth of B16 mouse melanoma cells expressing human Muc1 in C57BL/6 mice was effectively suppressed by the Muc1-HSP70 chimeric DNA vaccine. Our results reveal that the antitumor efficacy of the chimeric DNA vaccine was improved by the presence of HSP/70.
authors: Tumor Immunity Medical Research Center, College of Medicine, Seoul National University, Jongno-gu, Seoul 110-799, Republic of Korea.
authors: Dae-Han
authors: DH
authors: Choi
authors: Jong Kyu
authors: JK
authors: Woo
authors: Yun
authors: Y
authors: Choi
authors: Hye-Sook
authors: HS
authors: Seo
authors: Chul-Woo
authors: CW
authors: Kim
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007109:Immunity; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA