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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

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,...

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Main Authors: Yukinobu Kodama (Author), Mikiro Nakashima (Author), Tadayuki Nagahara (Author), Natsuko Oyama (Author), Junya Hashizume (Author), Hiroo Nakagawa (Author), Hitomi Harasawa (Author), Takahiro Muro (Author), Tomoaki Kurosaki (Author), Chikamasa Yamashita (Author), Mitsuru Hashida (Author), Takashi Kitahara (Author), Hitoshi Sasaki (Author), Shigeru Kawakami (Author), Tadahiro Nakamura (Author)
Format: Book
Published: MDPI AG, 2020-06-01T00:00:00Z.
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Summary: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-<span style="font-variant: small-caps;">l</span>-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.
Item Description:10.3390/pharmaceutics12060540
1999-4923

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