title: Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-λ2 or IL-29/IFN-λ1.
abstract: Interleukin (IL)-28A/interferon (IFN)-λ2 and IL-29/IFN-λ1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, we constructed an adenovirus vector expressing either IL-28A/IFN-λ2 (AdIL-28A) or IL-29/IFN-λ1 (AdIL-29) to evaluate the therapeutic properties of intratumoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections of either AdIL-28A or AdIL-29 when compared with AdNull. In vivo cell depletion experiments displayed that both NK cells and CD8(+) T cells have a major role in AdIL-28A-mediated tumor growth suppression. A significant increase in the number of infiltrating CD8(+) T cells into the tumors treated with either AdIL-28A or AdIL-29 was observed. Moreover, specific anti-tumor cytotoxic T lymphocyte reactivity was detected in spleen cells from animals treated with either AdIL-28A or AdIL-29. In IFN-γ-deficient mice, anti-tumor activities of AdIL-28A were completely impaired, indicating that IFN-γ is critically involved in the tumor growth inhibition triggered by AdIL-28A. IL-12 provided a synergistic anti-tumor effect when combined with AdIL-28A. These results indicate that AdIL-28A and AdIL-29 could be successfully utilized as an alternative cancer immunogene therapy.
authors: Laboratory of Clinical Science and Biomedicine, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
authors: K
authors: K
authors: Hasegawa
authors: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
authors: M
authors: M
authors: Tagawa
authors: Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: K
authors: K
authors: Takagi
authors: Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors: H
authors: H
authors: Tsukamoto
authors: Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors: Y
authors: Y
authors: Tomioka
authors: Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: T
authors: T
authors: Suzuki
authors: Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors: Y
authors: Y
authors: Nishioka
authors: Division of Geriatric Pharmacotherapy, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: T
authors: T
authors: Ohrui
authors: Laboratory of Clinical Science and Biomedicine, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
authors: M
authors: M
authors: Numasaki
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000235:genetics*; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000096:biosynthesis; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays; D000095022:Interferon Lambda
chemical_list: D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D007372:Interferons; D018664:Interleukin-12; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda