title: The induction of antigen-specific CTL by in situ Ad-REIC gene therapy.
abstract: An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ariyoshi
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Eikawa
authors.affiliation: Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Yamazaki
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sadahira
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Araki
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ebara
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nasu
authors.affiliation: Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Udono
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kumon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D018925:Chemokines; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D010047:Ovalbumin / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D010047:Ovalbumin
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