title: A loss of antitumor therapeutic activity of CEA DNA vaccines is associated with the lack of tumor cells' antigen presentation to Ag-specific CTLs in a colon cancer model.
abstract: Human colon cancers express carcinoembryonic antigen (CEA). Thus, CEA has been considered as a potential vaccine target for immune therapy against colon cancer. In this study, CEA DNA vaccines plus anti-4-1BB Abs treatment was found to increase Ag-specific CTL activity and antitumor protective responses to MC32 cells. However, CEA DNA vaccines alone displayed few antitumor therapeutic effects while significantly inducing Ag-specific CTL responses. Anti-4-1BB Abs alone displayed antitumor therapeutic effects. Intratumoral electroporation with IL-12 cDNA also showed antitumor therapeutic activity against MC32 cells in a CD8+ T cell-dependent and CEA-non-specific manner, suggesting that established MC32 cells are still susceptible to CTL-mediated killing. Finally, our in vitro assays (Western blot assay, IFN-γ, CTL and apoptosis assays, FACS analysis) and animal studies demonstrated that a lack of antitumor therapeutic activity of CEA DNA vaccines might result from acquisition of tumor cell resistance to Ag-specific CTL-mediated killing through the loss of tumor cells' antigen presentation to Ag-specific CTLs. Taken together, these data show that MC32 cells may resist CEA DNA vaccination by their loss of antigen presentation to CEA-specific CTLs in the therapeutic model.
authors.affiliation: BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Euri
authors.initials: E
authors.lastname: Ahn
authors.affiliation: BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Ha
authors.initials: H
authors.lastname: Kim
authors.affiliation: BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Kyusun Torque
authors.initials: KT
authors.lastname: Han
authors.affiliation: BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea. Electronic address: jsin1964@hanmail.net.
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Antitumor immunity; CEA; Colon cancer; DNA vaccines; Tumor immune evasion