Personalized immunochemotherapy for oral cancer basedon the genetic diagnosis

• Project/Area Number: 22390386
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Ehime University
• Principal Investigator: HAMAKAWA Hiroyuki 愛媛大学, 大学院・医学系研究科, 教授 (20127905)
• Co-Investigator(Kenkyū-buntansha): NAKASHIRO Koichi 愛媛大学, 大学院・医学系研究科, 准教授 (90314880)
• Co-Investigator(Renkei-kenkyūsha): OKAMOTO Masato 慶應大学, 医学部, 特任准教授 (10243718)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000); Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
• Keywords: 口腔癌 / 癌免疫療法 / 癌抗原 / OK-432 / 免疫療法 / 樹状細胞 / WT1

Research Abstract

Recently immunotherapy is a promising cancer therapy. And Dendritic cells (DC)-based vaccination is widely tested as a promising therapeutic cancer vaccine in multiple clinical trials. But there is no utility cancer antigen for oral cancer. We have identified Mucin 1 as a critical cancer antigen in oral cancer. Furthermore we conducted the in vitro experiments to examine whether or not chemotherapeutic drugs which are used for patients with oral cancer, may enhance T cell-stimulating ability of DCsvia regulation of the expression of PD-Ls. And then we identified IL-6, IL-8 and GCSFas a prognosis biomarker of oral cancer patients. The findings obtained from this study lead to development of personalized immunochemotherapy for oral cancer patients.

Research Products

• [Journal Article] Targeting Id1 reduces proliferation and invasion in aggressive human salivary gland cancer cells (2013)
  • Author(s): Sumida T, Murase R, Onishi-Ishikawa A, McAllister SD, Hamakawa H, Desprez PY
  • Journal Title: BMC Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Targeting Aurora kinase A suppresses the growth of human oral squamous cell carcinoma cells in vitro and in vivo. (2013)
  • Author(s): Tanaka H, Nakashiro K, Iwamoto K, Tokuzen N, Fujita Y, Shirakawa R, Oka R,Goda H, Hamakawa H
  • Journal Title: Oral Oncol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Combined TLR2/4-Activated Dendritic/Tumor Cell Fusions Induce Augmented Cytotoxic T Lymphocytes. (2013)
  • Author(s): Koido S, Homma S, Okamoto M, Namiki Y, Takakura K, Takahara A, Odahara S, Tsukinaga S, Yukawa T, Mitobe J, Matsudaira H, Nagatsuma K, Uchiyama K, Kajihara M, Arihiro S, Imazu H, Arakawa H, Kan S, Komita H, Ito M, Ohkusa T, Gong J, Tajiri H
  • Journal Title: PLoS One
  • Peer Reviewed
• [Journal Article] DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT). Impact of dendritic cell vaccines pulsed with Wilms' tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers. (2013)
  • Author(s): Takahashi H, Okamoto M, Shimodaira S, Tsujitani S, Nagaya M, Ishidao T, Kishimoto J, Yonemitsu Y
  • Journal Title: Eur J Cancer Volume: 49(4) Pages: 852-9
  • Peer Reviewed
• [Journal Article] Prognostic impact of expression of bcl-2 and bax genes in circulating immune cells derived from patients with head and neck carcinoma (2013)
  • Author(s): Tano T, Okamoto M, Kan S, Nakashiro K, Shimodaira S, Koido S, Homma S, Sato M,Fujita T, Kawakami Y, Hamakawa H.
  • Journal Title: Neoplasia Volume: 15(3) Pages: 305-14
  • Peer Reviewed
• [Journal Article] Epulis-like gingival angiosarcoma of the mandible: a case report. (2012)
  • Author(s): Sumida T, Murase R, Fujita Y, Ishikawa A, Hamakawa H.
  • Journal Title: Int J Clin Exp Pathol Volume: 5(8) Pages: 830-3
  • Peer Reviewed
• [Journal Article] Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro (2012)
  • Author(s): Kan S, Hazama S, Maeda K, Inoue Y, Homma S, Koido S, Okamoto M, Oka M
  • Journal Title: Anticancer Res Volume: 32(12) Pages: 5363-9
  • Peer Reviewed
• [Journal Article] Selective inhibition of NF-κB suppresses bone invasion by oral squamous cell carcinoma in vivo (2012)
  • Author(s): Furuta H, Osawa K, Shin M, Ishikawa A, Matsuo K, Khan M, Aoki K, Ohya K, Okamoto M, Tominaga K, Takahashi T, Nakanishi O, Jimi E.
  • Journal Title: Int J Cancer
  • Peer Reviewed
• [Journal Article] One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma (2012)
  • Author(s): Goda H, Nakashiro K, Oka R, Tanaka H, Wakisaka H, Hato N, Hyodo M, Hamakawa H.
  • Journal Title: Oral Oncol Volume: 48(10) Pages: 958-63
  • Peer Reviewed
• [Journal Article] Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes. (2012)
  • Author(s): Mayorca-Guiliani AE, Yano H, Nakashiro K, Hamakawa H, Tanaka J
  • Journal Title: Oral Oncol Volume: 48(8) Pages: 663-70
  • Peer Reviewed
• [Journal Article] Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines (2012)
  • Author(s): Tano T, Okamoto M, Kan S, Nakashiro K, Shimodaira S, Yamashita N, Kawakami Y, Hamakawa H.
  • Journal Title: Oral Oncol Volume: 48(8) Pages: 678-85
  • Peer Reviewed
• [Journal Article] Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in patients with advanced pancreatic carcinoma. (2012)
  • Author(s): Kimura Y, Tsukada J, Tomoda T, Takahashi H, Imai K, Shimamura K, Sunamura M, Yonemitsu Y, Shimodaira S, Koido S, Homma S, Okamoto M
  • Journal Title: Pancreas
  • Peer Reviewed
• [Journal Article] One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma (2012)
  • Author(s): Goda H
  • Journal Title: Oral Oncology Volume: 48 Pages: 958-63
  • DOI: 10.1016/j.oraloncology.2012.03.026
  • Peer Reviewed
• [Journal Article] Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes (2012)
  • Author(s): Mayorca-Guiliani AE
  • Journal Title: Oral Oncology Volume: 48 Pages: 663670-663670
  • DOI: 10.1016/j.oraloncology.2012.02.007
  • Peer Reviewed
• [Journal Article] Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines (2012)
  • Author(s): Tano T
  • Journal Title: Oral Oncol Volume: 48 Pages: 678-685
  • DOI: 10.1016/j.oraloncology.2012.02.005
  • Peer Reviewed
• [Journal Article] Premetastic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes (2012)
  • Author(s): Mayorca-Guilliani AE, Yano H, Nakashiro K, Hamakawa H, Tanaka J
  • Journal Title: Oral Oncology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines (2012)
  • Author(s): Tano T, Okamoto M, Kan S, Nakashiro K, Shimodaira S, Yamashita N, Kawakami Y, Hamakawa H
  • Journal Title: Oral Oncology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] The inhibition of RANKL/RANK signaling by osteoprotegerin suppresses bone invasion by oral squamous cell carcinoma cells. (2011)
  • Author(s): Shin M, Matsuo K, Tada T, Fukushima H, Furuta H, Ozeki S, Kadowaki T, Yamamoto K, Okamoto M, Jimi E
  • Journal Title: Carcinogenesis
  • Peer Reviewed
• [Journal Article] Increased telomerase activity and hTERT expression in human salivary gland carcinomas (2011)
  • Author(s): Shigeishi H, Sugiyama M, Tahara H, Ono S, Kumar Bhawal U, Okura M, Kogo M, Shinohara M, Shindoh M, Shintani S, Hamakawa H, Takata T, Kamata N.
  • Journal Title: Oncol Lett 1 Volume: 2(5) Pages: 845-850
  • Peer Reviewed
• [Journal Article] The Oral Cancer Study Group of Chugoku-Shikoku. Effects of a concurrent chemoradiotherapy with S-1 for locally advanced oral cancer (2011)
  • Author(s): Hino S, Hamakawa H, Miyamoto Y, Ryoke K, Sekine J, Sasaki A, Yamamoto T
  • Journal Title: Oncol Lett 1 Volume: 2(5) Pages: 839-843
  • Peer Reviewed
• [Journal Article] Novel therapeutic strategies for malignant salivary gland tumors: lessons learned from breast cancer (2011)
  • Author(s): Murase R, Sumida T, Ishikawa A, Murase R, McAllister SD, Hamakawa H, Desprez PY
  • Journal Title: International Journal of Otolaryngology
  • DOI: 10.1155/2011/187623
  • Peer Reviewed
• [Journal Article] Human FAT1 cadherin controls cell migration and invasion of oral squamous cell carcinoma through the localization of β-catenin. (2011)
  • Author(s): Nishikawa Y, Miyazaki T, Nakashiro K, Yamagata H, Isokane M, Goda H, Tanaka H, Oka R, Hamakawa H.
  • Journal Title: Oncol Rep Volume: 26(3) Pages: 587-92
  • Peer Reviewed
• [Journal Article] Gene therapy for oral squamous cell carcinoma with IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells (2011)
  • Author(s): Zhang T, Hamada K, Hyodo M, Itoh H, Tani K, Goda H, Nakashiro K, Hamakawa H
  • Journal Title: Oncol Rep Volume: 25(3) Pages: 795-802
  • Peer Reviewed
• [Journal Article] Silencing Id-1 inhibits lymphangiogenesis through down-regulation of VEGF-C in oral squamous cell carcinoma. (2011)
  • Author(s): Dong Z, Wei F, Zhou C, Sumida T, Hamakawa H, Hu Y, Liu S
  • Journal Title: Oral Oncol Volume: 47(1) Pages: 27-32
  • Peer Reviewed
• [Journal Article] Silencing Id-1 with RNA interference inhibits adenoid cystic carcinoma in mice (2011)
  • Author(s): Chen Z, Liu S, Sumida T, Sun S, Wei Y, Liu M, Dong Z, Zhang F, Hamakawa H, Wei F.
  • Journal Title: J Surg Res Volume: 169(1) Pages: 57-66
  • Peer Reviewed
• [Journal Article] Novel therapeutic strategies for malignant salivary gland tumors : lesson learned from breast cancer (2011)
  • Author(s): Murase R, Sumida T, Ishikawa A, Murase R, McAllister SD, Hamakawa H, Desprez PY
  • Journal Title: International Journal of Otolaryngology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Human FAT1 cadherin controls cell migration and invasion of oral squamous cell carcinoma through the localization of beta-catenin (2011)
  • Author(s): Nishikawa, Y.
  • Journal Title: Oncology Report Volume: 26(3) Pages: 587-592
  • DOI: 10.3892/or.2011.1324
  • Peer Reviewed
• [Journal Article] Gene therapy for head and neck squamous carcinoma cells by IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells (2011)
  • Author(s): Zhang T, et al
  • Journal Title: Oncol Rep Volume: 25 Pages: 795-802
  • Peer Reviewed
• [Journal Article] Silencing Id-1 inhibits lymphangiogenesis through down-regulation of VEGF-C in oral squamous cell carcinoma (2011)
  • Author(s): Dong Z, et al
  • Journal Title: Oral Oncol Volume: 47 Pages: 27-32
  • Peer Reviewed
• [Journal Article] Knockdown of Akt isoforms by RNA silencing suppresses the growth of human prostate cancer cells in vitro and in vivo. (2010)
  • Author(s): Sasaki T, Nakashiro K, Tanaka H, Azuma K, Goda H, Hara S, Onodera J, Fujimoto I, Tanji N, Yokoyama M, Hamakawa H
  • Journal Title: Biochem Biophys Res Commun 13 Volume: 399(1) Pages: 79-83
  • Peer Reviewed
• [Journal Article] Carrier cell-mediated cell lysis of squamous cell carcinoma cells by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus (2010)
  • Author(s): Hamada K, Zhang T, Desaki J, Nakashiro K, Itoh H, Tani K, Koyama Y, Hamakawa H
  • Journal Title: J Gene Med Volume: 12(6) Pages: 545-54
  • Peer Reviewed
• [Journal Article] Massive subcutaneous emphysema developing before surgery for mandibular fracture: a case report (2010)
  • Author(s): Sumida T, Kobayashi A, Oka R, Yorozuya T, Nagaro T, Hamakawa H
  • Journal Title: Dent Traumatol Volume: 26(4) Pages: 363-5
  • Peer Reviewed
• [Journal Article] Carrier cell-mediated cell lysis of squamous cell carcinoma cells by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus (2010)
  • Author(s): Hamada K, et al
  • Journal Title: J Gene Med Volume: 12 Pages: 545-554
  • Peer Reviewed
• [Presentation] 口腔扁平上皮癌における癌抗原 WT1 および MUC1 の発現 (2013)
  • Author(s): 藤田陽平、中城公一、合田啓之、田野智之、浜川裕之
  • Organizer: 第31回日本口腔腫瘍学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] 5-FU による樹状細胞の SOCS 発現の抑制と T 細胞活性化能の増強 (2012)
  • Author(s): 田野智之、岡本正人、合田啓之、藤田陽平、中城公一、浜川裕之
  • Organizer: 第60回日本口腔科学会中四国地方部会
  • Place of Presentation: 広島
  • Year and Date: 2012-10-06
• [Presentation] 本院における化学療法を併用したペプチドパルス樹状細胞がんワクチン療法の臨床試験 (2012)
  • Author(s): 岡本正人、藤田知信、河上 裕
  • Organizer: 第22回日本樹状細胞研究会
  • Place of Presentation: 福島
  • Year and Date: 2012-06-15
• [Presentation] 化学療法を併用した樹状細胞がんワクチン療法の臨床試験への取り組み (2012)
  • Author(s): 岡本正人、藤田知信、竹内裕也、船越 健、真柳修平、高石官均、田口淳一、砂村真琴、日比紀文、天谷雅行、北川雄光、河上 裕
  • Organizer: 第25回日本バイオセラピィ学会学術集会
  • Place of Presentation: 倉敷
• [Presentation] 化学療法剤による樹状細胞の SOCS-1, -2 発現の抑制と T 細胞活性化能の増強 (2012)
  • Author(s): 田野智之、岡本正人、合田啓之、藤田陽平、中城公一、浜川裕之
  • Organizer: 第25回日本バイオセラピィ学会学術集会
  • Place of Presentation: 倉敷
• [Presentation] 口腔癌SNNSの検証と新戦略 (2011)
  • Author(s): 浜川裕之
  • Organizer: 第13回SNNS研究会学術集会
  • Place of Presentation: 浜離宮朝日ホール・東京
  • Year and Date: 2011-12-03
• [Presentation] 樹状細胞がんワクチンの現状 (2011)
  • Author(s): 岡本正人
  • Organizer: 第49回日本癌治療学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 成熟樹状細胞の貪食能ならびに樹状細胞局所投与療法への応用に関する検討 (2011)
  • Author(s): 岡本正人、塚田 旬 、カンシン、木村 幸乃
  • Organizer: 第49回日本癌治療学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 治療経験のある進行膵癌に対する樹状細胞ワクチン療法～臨床的・免疫学的検討～ (2011)
  • Author(s): 岡本正人、木村幸乃、今井一弘、嶋村香苗、塚田 旬、石田尾武文、高橋秀徳、砂村真琴、下平繁隆、小井戸繁雄、本間 定
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] Immuno-chemoradiotherapy for head and neck cancer: Augmentation of OK-432- induced anti-tumor immunity by tegafur and radiation. (2011)
  • Author(s): Okamoto M, Tano T, Kan S, Sato M.
  • Organizer: 102ndAmerican Association for Cancer Research Annual Meeting
  • Place of Presentation: Orlando, FL
• [Presentation] 樹状細胞を用いた癌ワクチン療法～基礎から臨床へ～ (2011)
  • Author(s): 岡本正人
  • Organizer: 第29回日本口腔腫瘍学会総会
  • Place of Presentation: 熊本
• [Presentation] One-step nucleic acid amplification (OSNA) method for detecting metastasis of oral cancer (2010)
  • Author(s): 浜川裕之
  • Organizer: The 7^<th> International Sentinel Node Meeting
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-11-20
• [Patent(Industrial Property Rights)] アンドロゲン受容体遺伝子に特異的な siRNA (2012)
  • Inventor(s): 中城公一、浜川裕之
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Acquisition Date: 2012-04-06
• [Patent(Industrial Property Rights)] 頭頸部癌の腫瘍マーカー (2012)
  • Inventor(s): 中城公一、浜川裕之
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Acquisition Date: 2012-04-13
• [Patent(Industrial Property Rights)] ADAT1 遺伝子に特異的な siRNA (2012)
  • Inventor(s): 中城公一、浜川裕之
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Acquisition Date: 2012-10-12
• [Patent(Industrial Property Rights)] マイクロ RNA 又はその発現系を含む組成物 (2011)
  • Inventor(s): 中城公一、浜川裕之、田中宏史
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Industrial Property Number: 2011-113348
  • Filing Date: 2011-05-20
• [Patent(Industrial Property Rights)] マイクロRNA又はその発現系を含む組成物 (2011)
  • Inventor(s): 中城公一、浜川裕之、田中宏史
  • Industrial Property Rights Holder: 愛媛大学
  • Industrial Property Number: 2011-113348
  • Filing Date: 2011-05-20
• [Patent(Industrial Property Rights)] マイクロRNAのアンチセンスオリゴヌクレオチドを含む組成物 (2010)
  • Inventor(s): 中城公一、浜川裕之、田中宏史
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Industrial Property Number: 2010-254021
  • Filing Date: 2010-11-12
• [Patent(Industrial Property Rights)] マイクロRNAのアンチセンスオリゴヌクレオチドを含む組成物 (2010)
  • Inventor(s): 中城公一, 浜川裕之, 田中宏史
  • Industrial Property Rights Holder: 愛媛大学
  • Industrial Property Number: 2010-254021
  • Filing Date: 2010-11-12