Suppression of breast cancer metastasis using the next generation nasal spray vaccine

• Project/Area Number: 25670441
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Mie University
• Principal Investigator: KAWANO Mitsuo 三重大学, 医学(系)研究科(研究院), 講師 (00234097)
• Co-Investigator(Kenkyū-buntansha): KATO Takuma 三重大学, 大学院医学系研究科, 准教授 (60224515)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: hPIV2 / 乳癌 / 遺伝子免疫療法 / 腫瘍免疫 / 免疫活性化 / 細胞性免疫 / 液性免疫 / 転移 / PIV2 / 生体制御

Outline of Final Research Achievements

Recently, we have established a novel functional replication-deficient virus vector; a recombinant human parainfluenza type 2 virus vector (hPIV2): highly safe, expressive and immunogenic vector.
In this study, we have developed hPIV2 engineered to express Ag85B (hPIV2/Ag85B) and investigated antitumor effects against breast cancer metastasis by intranasal administration to a breast cancer like model mice generated by transplanting 4T1-Luc cells using the hPIV2/Ag85B. Especially, suppression effects of breast cancer metastasis were recognized in mouse lungs vaccinated high dose hPIV2/Ag85B.

Research Products

• [Journal Article] Ribavirin inhibits human parainfluenza virus type 2 replication in vitro. (2014)
  • Author(s): Kihira S, Uematsu J, Kawano M, Itoh A, Ookohchi A, Satoh S, Maeda Y, Sakai K, Yamamoto H, Tsurudome M, O'Brien M, Komada H.
  • Journal Title: Microbiol Immunol. Volume: 58 Issue: 11 Pages: 628-635
  • DOI: 10.1111/1348-0421.12192
  • NAID: 40020271490
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation. (2014)
  • Author(s): Nishikawa K, Seo N, Torii M, Ma N, Muraoka D, Tawara I, Masuya M, Tanaka K, Takei Y, Shiku H, Katayama N, Kato T.
  • Journal Title: PLoS One. Volume: 9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vero/BC-F: an efficient packaging cell line stably expressing F protein to generate single round-infectious human parainfluenza virus type 2 vector. (2014)
  • Author(s): Ohtsuka J, Fukumura M, Tsurudome M, Hara K, Nishio M, Kawano M, Nosaka T.
  • Journal Title: Gene Ther Volume: 21 Issue: 8 Pages: 775-784
  • DOI: 10.1038/gt.2014.55
  • Peer Reviewed
• [Journal Article] Recombinant Ag85B vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed Mycobacteria-specific immune responses by intranasal immunization. (2014)
  • Author(s): Watanabe K, Matsubara A, Kawano M, Mizuno S, Okamura T, Tsujimura Y, Inada H, Nosaka T, Matsuo K, Yasutomi Y.
  • Journal Title: Vaccine Volume: 32 Issue: 15 Pages: 1727-1735
  • DOI: 10.1016/j.vaccine.2013.11.108
  • Peer Reviewed
• [Journal Article] Intranasally administered antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis. (2013)
  • Author(s): Kitagawa H, Kawano M, Yamanaka K, Kakeda M, Tsuda K, Inada H, Yoneda M, Sakaguchi T, Nigi A, Nishimura K, Komada H, Tsurudome M, Yasutomi Y, Nosaka T, Mizutani H.
  • Journal Title: PLoS One. Volume: 8 Issue: 7 Pages: 66614-66614
  • DOI: 10.1371/journal.pone.0066614
  • Peer Reviewed
• [Journal Article] Human Parainfluenza virus type 2 vector induces dendritic cell maturation without viral RNA replication/transcription. (2013)
  • Author(s): Hara K, Fukumura M, Ohtsuka J, Kawano M, Nosaka T.
  • Journal Title: Hum Gene Ther Volume: 24 Issue: 7 Pages: 683-691
  • DOI: 10.1089/hum.2013.024
  • Peer Reviewed
• [Journal Article] Full conversion of the hemagglutinin-neuraminidase specificity of the parainfluenza virus 5 fusion protein by replacement of 21 amino acids in its head region with those of the simian virus 41 fusion protein. (2013)
  • Author(s): Tsurudome M, Nakahashi M, Matsushima Y, Ito M, Nishio M, Kawano M, Komada H, Nosaka T.
  • Journal Title: J. Virol. Volume: 87 Issue: 15 Pages: 8342-8350
  • DOI: 10.1128/jvi.03549-12
  • Peer Reviewed
• [Presentation] カスパーゼ阻害剤Z-VAD-FMKのパラインフルエンザウイルス２型増殖への作用 (2015)
  • Author(s): 植松 淳、酒井香江、鈴木沙織、吉見由美子、山本秀孝、河野光雄、鶴留雅人、駒田 洋
  • Organizer: 日本薬学会第135年回
  • Place of Presentation: デザイン・クリエイティブセンター神戸（神戸）
  • Year and Date: 2015-03-28
• [Presentation] フラボノイドのパラインフルエンザウイルス２型増殖への作用 (2015)
  • Author(s): 酒井香江、植松 淳、山本秀孝、河野光雄、鶴留雅人、駒田 洋
  • Organizer: 日本薬学会第135年回
  • Place of Presentation: デザイン・クリエイティブセンター神戸（神戸）
  • Year and Date: 2015-03-28
• [Presentation] ヒトと同様の発現様式を示す癌胎児性抗原（CEA）トランスジェニックマウスを用いたCEA特異的キメラ抗原受容体導入T細胞輸注療法の有効性と安全性の検討 (2014)
  • Author(s): 王立楠、加藤琢磨、瀬尾尚宏、岡本幸子、天石泰典、峰野純一、竹迫一任、珠玖洋
  • Organizer: 日本がん免疫学会
  • Place of Presentation: ひめぎんホール（松山）
  • Year and Date: 2014-07-30 – 2014-08-01
• [Presentation] グリチルリチン酸によるパラインフルエンザウイルス２型増殖阻害 (2014)
  • Author(s): 山本秀孝、鎌田未有紀、谷口弘恵、植松淳、河野光雄、鶴留雅人、伊藤眞、駒田洋
  • Organizer: 日本薬学会第１３４年会
  • Place of Presentation: 熊本市総合体育館
• [Presentation] パラインフルエンザウイルスのHN蛋白とF蛋白の機能的相互作用の解析 (2013)
  • Author(s): 鶴留雅人、伊藤守弘、西尾真知子、河野光雄、駒田洋、大塚順平、野阪哲哉
  • Organizer: 日本ウイルス学会
  • Place of Presentation: 神戸国際会議場