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Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues


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Title: Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues
Authors: Kodama, Yukinobu / Nakashima, Mikiro / Nagahara, Tadayuki / Oyama, Natsuko / Hashizume, Junya / Nakagawa, Hiroo / Harasawa, Hitomi / Muro, Takahiro / Kurosaki, Tomoaki / Yamashita, Chikamasa / Hashida, Mitsuru / Kitahara, Takashi / Sasaki, Hitoshi / Kawakami, Shigeru / Nakamura, Tadahiro
Issue Date: 11-Jun-2020
Publisher: MDPI
Citation: Pharmaceutics, 12(6), art.no.540; 2020
Abstract: The present study investigated a pulmonary delivery system of plasmid DNA (pDNA) and its application to melanoma DNA vaccines. pCMV-Luc, pEGFP-C1, and pZsGreen were used as a model pDNA to evaluate transfection efficacy after inhalation in mice. Naked pDNA and a ternary complex, consisting of pDNA, dendrigraft poly-L-lysine (DGL), and γ-polyglutamic acid (γ- PGA), both showed strong gene expression in the lungs after inhalation. The transgene expression was detected in alveolar macrophage-rich sites by observation using multi-color deep imaging. On the basis of these results, we used pUb-M, which expresses melanoma-related antigens (ubiquitinated murine melanoma gp100 and tyrosinase-related protein 2 (TRP2) peptide epitopes), as DNA vaccine for melanoma. The inhalation of naked pUb-M and its ternary complex significantly inhibited the metastasis of B16-F10 cells, a melanoma cell line, in mice. The levels of the inflammatory cytokines, such as TNF-α, IFN-γ, and IL-6, which enhance Th1 responses, were higher with the pUb-M ternary complex than with naked pUb-M and pEGFP-C1 ternary complex as control. In conclusion, we clarified that the inhalation of naked pDNA as well as its ternary complex are a useful technique for cancer vaccination.
Keywords: DNA vaccine / Gene delivery / Inhalation / Melanoma / Ternary complex
URI: http://hdl.handle.net/10069/40073
DOI: 10.3390/pharmaceutics12060540
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/40073

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