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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

1
Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
2
Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan
3
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
4
Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan
5
Department of Pharmacy, Yamaguchi University Hospital, 1-1-1 MinamiKogushi, Ube, Yamaguchi 755-8505, Japan
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 540; https://doi.org/10.3390/pharmaceutics12060540
Received: 6 May 2020 / Revised: 7 June 2020 / Accepted: 9 June 2020 / Published: 11 June 2020
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. View Full-Text
Keywords: gene delivery; inhalation; DNA vaccine; ternary complex; melanoma gene delivery; inhalation; DNA vaccine; ternary complex; melanoma
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MDPI and ACS Style

Kodama, Y.; Nakashima, M.; Nagahara, T.; Oyama, N.; Hashizume, J.; Nakagawa, H.; Harasawa, H.; Muro, T.; Kurosaki, T.; Yamashita, C.; Hashida, M.; Kitahara, T.; Sasaki, H.; Kawakami, S.; Nakamura, T. 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. Pharmaceutics 2020, 12, 540. https://doi.org/10.3390/pharmaceutics12060540

AMA Style

Kodama Y, Nakashima M, Nagahara T, Oyama N, Hashizume J, Nakagawa H, Harasawa H, Muro T, Kurosaki T, Yamashita C, Hashida M, Kitahara T, Sasaki H, Kawakami S, Nakamura T. 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. Pharmaceutics. 2020; 12(6):540. https://doi.org/10.3390/pharmaceutics12060540

Chicago/Turabian Style

Kodama, Yukinobu, Mikiro Nakashima, Tadayuki Nagahara, Natsuko Oyama, Junya Hashizume, Hiroo Nakagawa, Hitomi Harasawa, Takahiro Muro, Tomoaki Kurosaki, Chikamasa Yamashita, Mitsuru Hashida, Takashi Kitahara, Hitoshi Sasaki, Shigeru Kawakami, and Tadahiro Nakamura. 2020. "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" Pharmaceutics 12, no. 6: 540. https://doi.org/10.3390/pharmaceutics12060540

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