Development of a novel cancer vaccine that targets oral cancer stem cells

• Project/Area Number: 24659901
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Sapporo Medical University
• Principal Investigator: HIRATSUKA Hiroyoshi 札幌医科大学, 医学部, 教授 (50165180)
• Co-Investigator(Kenkyū-buntansha): DEHARI Hironari 札幌医科大学, 医学部, 講師 (00381260) ; MIYAZAKI Akihiro 札幌医科大学, 医学部, 准教授 (10305237) ; OGI Kazuhiro 札幌医科大学, 医学部, 講師 (40433114) ; MICHIFURI Yoshitaka 札幌医科大学, 医学部, 研究員 (00457722)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 口腔がん / がん幹細胞 / がんワクチン / ALDH1 / ワクチン / 幹細胞

Outline of Final Research Achievements

Oral cancer stem cells were isolated from oral cancer cell lines as aldehyde dehydrogenase 1 bright (ALDH1br) cells using the ALDEFLUOR assay. Expression of cancer stem cell-associated genes is increased in ALDH1br cells with a strong carcinogenesis and a high proliferative capacity. The small proline-rich protein-1B (SPRR1B) gene was shown to be overexpressed in ALDH1br cells. SPRR1B gene knockdown decreased the ALDH1br cell population and its proliferative capacity. Expression of the tumor suppressor gene Ras association domain family member 4 (RASSF4) was found to be suppressed in cells overexpressing SPRR1B. Our results suggest that oral cancer stem cells isolated as ALDH1br cells and SPRR1B have a role in cell growth by the suppression of RASSF4.

Research Products

• [Journal Article] Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer stem-like cells and is related to their growth through activation of MAP kinase signal. (2013)
  • Author(s): Michifuri Y, Hirohashi Y, Torigoe T, Miyazaki A, Fujino J, Tamura Y, Tsukahara T, Kanaseki T, Kobayashi J, Sasaki T, Takahashi A, Nakamori K, Yamaguchi A, Hiratsuka H, Sato N.
  • Journal Title: Biochem Biophys Res Commun Volume: 439 Issue: 1 Pages: 96-102
  • DOI: 10.1016/j.bbrc.2013.08.021
  • Peer Reviewed
• [Journal Article] Six-transmembrane epithelial antigen of the prostate-1 plays a role for in vivo tumor growth via intercellular communication (2013)
  • Author(s): Yamamoto T, Tamura Y, Kobayashi J, Kamiguchi K, Hirohashi Y, Miyazaki A, Torigoe T, Asanuma H, Hiratsuka H, Sato N
  • Journal Title: Exp. Cell Res. Volume: 319 Issue: 17 Pages: 2617-29
  • DOI: 10.1016/j.yexcr.2013.07.025
  • Peer Reviewed
• [Journal Article] Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia. (2013)
  • Author(s): Shimanishi M, Ogi K, Sogabe Y, Kaneko T, Dehari H, Miyazaki A, Hiratsuka H.
  • Journal Title: J Oral Pathol Med. Volume: 42(5) Issue: 5 Pages: 382-8
  • DOI: 10.1111/jop.12028
  • Peer Reviewed
• [Journal Article] Highexpression of ALDH1 and SOX2 diffuse staining pattern of oral squamous cellcarcinomas correlates to lymph node metastasis. (2013)
  • Author(s): Michifuri Y, Hirohashi Y, Torigoe T,Miyazaki A, Kobayashi J, Sasaki T, FujinoJ, Asanuma H, Tamura Y, Nakamori K, Hasegawa T, Hiratsuka H, Sato N.
  • Journal Title: Pathol Int. Volume: 62(10) Issue: 10 Pages: 684-9
  • DOI: 10.1111/j.1440-1827.2012.02851.x
  • Peer Reviewed
• [Journal Article] 口腔悪性腫瘍 (2012)
  • Author(s): 宮崎晃亘
  • Journal Title: 医学と薬学 Volume: 67 Pages: 799-805
• [Journal Article] General rules for clinical and pathological studies on oral cancer (2012)
  • Author(s): Izumo T
  • Journal Title: Jpn J Clin Oncol. Volume: 42 Pages: 1099-1109
• [Journal Article] Granulocyte colony-stimulating factor-producing squamous cellcarcinoma of the lower gingiva: a case report. (2012)
  • Author(s): Kobayashi J, Miyazaki A, Yamamot T, Nakamori K, Suzuki R, Kaneko T, Suzuki N, Hiratsuka H.
  • Journal Title: Head Neck Oncol. Volume: 4 Issue: 1 Pages: 35-35
  • DOI: 10.1186/1758-3284-4-35
  • Peer Reviewed
• [Presentation] Immunotherapeutic benefit of α-interferon in survivin2B-derived peptide vaccination for patients with oral cancer. (2014)
  • Author(s): Akihiro Miyazaki, Junichi Kobayashi, Toshihiko Torigoe, Yoshihiko Hirohashi, Takanori Sasaki, Sho Miyamoto, Kazuhiro Ogi, Hironari Dehari, Noriyuki Sato, Hiroyoshi Hiratsuka
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-28
• [Presentation] Tumor cells exposed to microenvironmental stresses express non-classical MHC Ib that attenuates CD8+ T cell responses (2014)
  • Author(s): Takanori Sasaki, Takayuki Kanaseki, Sachiyo Kawami, Eri Saka, Yasuaki Tamura, Toshihiko Torigoe, Hiroyoshi Hiratsuka, Noriyuki Sato
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-28
• [Presentation] A next-Generation Sequencing Screen for Mutational Hotspots in 50 Cancer-Related Genes using Semiconductor Sequencer. (2014)
  • Author(s): Takafumi Nakagaki, Yasushi Sasaki, Masashi Idogawa, Kousuke Takeda, Miyuki Tamura, Tomoko Ohashi, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-28
• [Presentation] Identification of the natural antigenic peptide derived from FAM83B that is specifically expressed in cancer stem cells. (2014)
  • Author(s): Sho Miyamoto, Takayuki Kanaseki, Akari Takahashi, Kochin Vitaly, Yoshihiko Hirohashi, Toshihiko Torigoe, Hiroyoshi Hiratsuka, Noriyuki Sato
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-28
• [Presentation] Identification of long non-coding RNAs potentially involved in oral squamous cell carcinoma. (2014)
  • Author(s): Koyo Nishiyama, Reo Maruyama, Kosuke Takeda, Takahumi Nakagaki, Takeshi Niinuma, Kazuhiro Ogi, Hironari Dehari, Akihiro Miyazaki, Masahiro Kai, Yasushi Sasaki, Takeshi Tokino, Hiromu Suzuki, Hiroyoshi Hiratsuka
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-28
• [Presentation] Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 family target (2014)
  • Author(s): Kousuke Takeda，Yasushi Sasaki , Takafumi Nakagaki, Miyuki Tamura, Masashi Idogawa , Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Wnt/β-catenin signaling pathway directly controls hypoxia induced epithelial mesenchymal transition in oral cancer (2014)
  • Author(s): Takeshi Kaneko, Hironari Dehari, Kazuhiro Ogi, Kousuke Takeda, Junichi Kobayashi, Akihiro Miyazaki, Hiroyoshi Hiratsuka
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 口腔がんに対するサバイビン２Bペプチドワクチン・インターフェロン併用療法の臨床試験 (2014)
  • Author(s): 宮崎晃亘、小林淳一、鳥越俊彦、廣橋良彦、佐々木敬則、宮本昇、出張裕也、荻和弘、佐藤昇志、平塚博義
  • Organizer: 第５２回日本癌治療学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] StageI,II口腔扁平上皮癌の治療成績の検討 (2013)
  • Author(s): 五十嵐友彦
  • Organizer: 第37回日本頭頸部癌学会
  • Place of Presentation: 東京
• [Presentation] 進行・再発口腔がんに対するｱｼﾞｭﾊﾞﾝﾄ併用survivin-2Bﾍﾟﾌﾟﾁﾄﾞﾜｸﾁﾝ療法 (2013)
  • Author(s): 宮崎晃亘
  • Organizer: 第37回日本頭頸部癌学会
  • Place of Presentation: 東京
• [Presentation] 口腔癌に対するCDDPを用いた放射線併用選択的動注化学療法の検討 (2013)
  • Author(s): 小林淳一
  • Organizer: 第37回日本頭頸部癌学会
  • Place of Presentation: 東京
• [Presentation] Tumor cells exposed to microenvironmental stresses express non-classical MHC class Ib that attenuates CD8+ T cell responses (2013)
  • Author(s): Takanori Sasaki
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] The Wnt/β-catenin signaling pathway directly controls hypoxia-induced epitelial-mesenchymal transition in oral cancer. (2013)
  • Author(s): Takeshi Kaneko
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Identification and characterization of the intercellular adhesion molecule-2 (ICAM2) gene as a novel p53 family target. (2013)
  • Author(s): Kousuke Takeda
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 口腔がんに対するアジュバント併用survivin-2Bペプチドワクチン療法の臨床・免疫学的効果 (2012)
  • Author(s): 宮崎晃亘
  • Organizer: 第66回 日本口腔科学会学術集会
  • Place of Presentation: 広島
• [Presentation] 小胞体ストレス下で提示される新規MHCI抗原ペプチド群の解析 (2012)
  • Author(s): 佐々木敬則
  • Organizer: 第66回 日本口腔科学会学術集会
  • Place of Presentation: 広島
• [Presentation] 口蓋に発生した多形腺腫由来筋上皮癌の１例 (2012)
  • Author(s): 竹田康佑
  • Organizer: 第66回 日本口腔科学会学術集会
  • Place of Presentation: 広島
• [Presentation] Sliencing of GLUT1 inhibits sensitizes oral cancer cells to CDDP during hypixia (2012)
  • Author(s): 荻 和弘
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Survivin-dirived peptide vaccine therapy for patients with advanced or recurrent oral cancer-Phase I clinical trial (2012)
  • Author(s): 宮崎晃亘
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Book] Tongue: Anatomy, Kinematics and Diseases (2012)
  • Author(s): Nakamori K
  • Total Pages: 233
  • Publisher: Nova Science Publishers, Inc
• [Remarks] 札幌医科大学医学部口腔外科学講座 悪性腫瘍
  • URL: http://web.sapmed.ac.jp/oral/guide/special/m16l6f00000002fm.html