Development of a novel therapeutic vaccine for precursor lesion of cervical cancer using mucosal immunity

• Project/Area Number: 20591938
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: KAWANA Kei The University of Tokyo, 医学部附属病院, 助教 (60311627)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 子宮頸癌 / 前癌病変 / 乳酸菌ワクチン / CD1d / iNKT細胞 / ヒトパピローマウイルス(HPV) / 子宮頸癌治療ワクチン / HPV E7蛋白質 / 粘膜免疫 / 子宮頸部リンパ球

Research Abstract

Mucosal cellular immunity against HPV is necessary for clearance of precursor lesion of cervical cancer (CIN3) since CIN develops in the mucosal epithelium at cervix. This study demonstrated a strategy to induce mucosal anti-HPV cellular immune responses into the cervical mucosa and we started Phase I/IIa clinical trial of a novel therapeutic vaccine for treatment of CIN3 as a translational research.

Research Products

• [Journal Article] Introducing HPV vaccine and scaling up screening procedures to prevent deaths from cervical cancer in Japn : A cost-effectiveness analysis. (2011)
  • Author(s): Yamamoto N, Mori R, Jacklin P, Osuga Y, Kawana K, Shibuya K, Taketani Y
  • Journal Title: Int.J Obstet and Gynecol (in-press)
  • Peer Reviewed
• [Journal Article] Characterization of intraepithelial lymphocytes (IELs) residing in the cervical mucosa of patients with human papillomavirus (HPV)-infected intraepithelial neoplastic lesions. (2011)
  • Author(s): Kojima S, Kawana K, Fujii T, Yokoyama T, Miura S, Tomio K, Tomio A, Yamashita A, Adachi K, Sato H, Nagamatsu T, Schust DJ, Kozuma S, Taketani Y
  • Journal Title: Am J Reprod Immunol (in-press)
  • Peer Reviewed
• [Journal Article] A possible coagulation-independent mechanism for pregnancy 1 loss involving β2glycoprotein 1-dependent antiphospholipid antibodies and CD1d. (2011)
  • Author(s): Iwasawa Y, Kawana K, Fujii T, Schust DJ, Nagamatsu T, Kawana Y, Sayama S, Miura S, Matsumoto J, Adachi K, Hyodo H, Yamashita T, Kozuma S, Taketani Y
  • Journal Title: Am J Reprod Immunol (in-press)
  • Peer Reviewed
• [Journal Article] Interstitial pneumonitis induced by pegylated liposomal doxorubicin in a patient with recurrent ovarian cancer. (2011)
  • Author(s): Inaba K, Arimoto T, Hoya M, Kawana K, Nakagawa S, Kozuma S, Taketani Y
  • Journal Title: Med Oncol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Second-line chemotherapy with docetaxel and carboplatin in paclitaxel and platinum-pretreated ovarian, fallopian tube, and peritoneal cancer. (2011)
  • Author(s): Arimoto T , Nakagawa S, Oda K, Kawana K, Yasugi T, Taketani Y
  • Journal Title: Med Oncol. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein : a possible mechanism for immune evasion by HPV. (2010)
  • Author(s): Miura S, Kawana K, Schust DJ, Fujii T, Yokoyama T, Iwasawa Y, Nagamatsu T, Adachi K, Tomio A, Tomio K, Kojima S, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: J Virol 84 Pages: 11614-11623
  • Peer Reviewed
• [Journal Article] Advanced age is a significant determinant of poor prognosis in patients treated with surgery plus postoperative radiotherapy for endometrial cancer. (2010)
  • Author(s): Okuma K, Yamashita H, Kawana K, Nakagawa S, Oda K, Nakagawa K
  • Journal Title: J Obstet Gynecol Res 36 Pages: 757-763
  • NAID: 10031121690
  • Peer Reviewed
• [Journal Article] Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma : a case report. (2010)
  • Author(s): Shoji K, Oda K, Nakagawa S, Kawana K, Yasugi T, Ikeda Y, Takazawa Y, Kozuma S, Taketani Y.
  • Journal Title: Med Oncol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Oral immunization with Lactobacillus casei vaccine expressing human papillomavirus (HPV) type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocyte against HPV16 E7. (2010)
  • Author(s): Adachi K, Kawana K, Yokoyama T, Fujii T, Tomio A, Miura S, Tomio K, Kojima S, Oda K, Sewaki T, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Vaccine 28 Pages: 2810-2817
  • Peer Reviewed
• [Journal Article] Comparison Between Conventional Surgery Plus Postoperative Adjuvant Radiotherapy and Concurrent Chemoradiation for FIGO Stage IIB Cervical Carcinoma : A Retrospective Study. (2010)
  • Author(s): Yamashita H, Okuma K, Kawana K, Nakagawa S, Oda K, Yano T, Kobayashi S, Wakui R, Ohtomo K, Nakagawa K.
  • Journal Title: Am J Clin Oncol 33 Pages: 583-586
  • Peer Reviewed
• [Journal Article] CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein : a possible mechanism for immune evasion by HPV. (2010)
  • Author(s): Miura S, Kawana K, Schust DJ, Fujii T, Yokoyama T, Iwasawa Y, Nagamatsu T, Adachi K, Tomio A, Tomio K, Kojima S, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Journal of Virology Volume: 84 Pages: 11614-11623
  • Peer Reviewed
• [Journal Article] Oral immunization with Lactobacillus casei vaccine expressing human papillomavirus (HPV) type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocyte against HPV16 E7. (2010)
  • Author(s): Adachi K, Kawana K, Yokoyama T, Fujii T, Tomio A, Miura S, Tomio K, Kojima S, Oda K, Sewaki T, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Vaccine Volume: 28 Pages: 2810-2817
  • Peer Reviewed
• [Journal Article] Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma : a case report. (2010)
  • Author(s): Shoji K, Oda K, Nakagawa S, Kawana K, Yasugi T, Ikeda Y, Takazawa Y, Kozuma S, Taketani Y.
  • Journal Title: Medical Oncology Volume: 31(E-pub)
  • Peer Reviewed
• [Journal Article] Advanced age is a significant determinant of poor prognosis in patients treated with surgery plus postoperative radiotherapy for endometrial cancer (2010)
  • Author(s): Okuma K, Yamashita H, Kawana K, Nakagawa S, Oda K, Nakagawa K
  • Journal Title: J Obstet Gynecol Res Volume: 36 Pages: 757-763
  • NAID: 10031121690
  • Peer Reviewed
• [Journal Article] Comparison Between Conventional Surgery Plus Postoperative Adjuvant Radiotherapy and Concurrent Chemoradiation for FIGO Stage IIB Cervical Carcinoma : A Retrospective Study. (2010)
  • Author(s): Yamashita H, Okuma K, Kawana K, Nakagawa S, Oda K, Yano T, Kobayashi S, Wakui R, Ohtomo K, Nakagawa K
  • Journal Title: Am J Clin Oncol Volume: 15(E-pub)
  • Peer Reviewed
• [Journal Article] Oral immunization with Lactobacillus casei vaccine expressing human papillomavirus(HPV)type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocyte against HPV16 E7 (2010)
  • Author(s): Adachi K, Kawana K, Yokoyama T, Fujii T, Tomio A, Miura S, Tomio K, Kojima S, Oda K, Sewaki T, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Vaccine 28 Pages: 2810-2817
  • Peer Reviewed
• [Journal Article] Comparison Between Conventional Surgery Plus Postoperative Adjuvant Radiotherapy and Concurrent Chemoradiation for FIGO Stage IIB Cervical Carcinoma : A Retrospective Study. (2010)
  • Author(s): Yamashita H, Okuma K, Kawana K, Nakagawa S, Oda K, Yano T, Kobayashi S, Wakui R, Ohtomo K, Nakagawa K.
  • Journal Title: Am J Clin Oncol (E-pub)
  • Peer Reviewed
• [Journal Article] Human papillomavirus vaccines : current issues and future : Review. (2009)
  • Author(s): Kawana K, Yasugi T, Taketani Y
  • Journal Title: Indian J Med Res 130 Pages: 341-347
  • Peer Reviewed
• [Journal Article] Identification of nucleolin as a protein that binds to human papillomavirus type 16 DNA. (2009)
  • Author(s): Sato H, Kusumoto-Matsuo R, Ishii Y, Mori S, Nakahara T, Shinkai-Ouchi F, Kawana K, Fujii T, Taketani Y, Kanda T, Kukimoto I
  • Journal Title: Biochem Biophys Res Commun 387 Pages: 525-530
  • Peer Reviewed
• [Journal Article] Expression of autotaxin, an ectoenzyme that produces lysophosphatidic acid, in human placenta. (2009)
  • Author(s): Iwasawa Y, Fujii T, Nagamatsu T, Kawana K, Okudaira S, Miura S, Matsumoto J, Tomio A, Hyodo H, Yamashita T, Oda K, Kozuma S, Aoki J, Yatomi Y, Taketani Y
  • Journal Title: Am J Reprod Immunol 62 Pages: 90-95
  • Peer Reviewed
• [Journal Article] The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. (2009)
  • Author(s): Shoji K, Oda K, Nakagawa S, Hosokawa S, Nagae G, Uehara Y, Sone K, Miyamoto Y, Hiraike H, Hiraike-Wada O, Nei T, Kawana K, Kuramoto H, Aburatani H, Yano T, Taketani Y.
  • Journal Title: Br J Cancer 101 Pages: 145-148
  • Peer Reviewed
• [Journal Article] Effect of progesterone on HLA-E gene expression in JEG-3 choriocarcinoma cell line. (2009)
  • Author(s): Huang Z, Hyodo H, Fujii T, Nagamatsu T, Matsumoto J, Kawana K, Yamashita T, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Am J Reprod Immunol 61 Pages: 221-226
  • Peer Reviewed
• [Journal Article] Expression of autotaxin, an ectoenzyme that produces lysophosphatidicacid, in human placenta. (2009)
  • Author(s): Iwasawa Y, Fujii T, Nagamatsu T, Kawana K, Okudaira S, Miura S, Matsumoto J, Tomio A, Hyodo H, Yamashita T, Oda K, Kozuma S, Aoki J, Yatomi Y, Taketani Y
  • Journal Title: Am J Reprod Immunol 62 Pages: 90-95
  • Peer Reviewed
• [Journal Article] Expression of CD1d and ligand-induced cytokine production are tissue-specific in mucosal epithelia of the human lower reproductive tract. (2008)
  • Author(s): Kawana K, Matsumoto J, Miura S, Shen L, Kawana Y, Nagamatsu T, Yasugi T, Fujii T, Yang H, Quayle AJ, Taketani Y, Schust DJ
  • Journal Title: Infect Immun 76 Pages: 3011-3018
  • Peer Reviewed
• [Journal Article] Expression of surface CD1d in the extra-villous trophoblast cells of early gestation placenta is downregulated through TGF-・1 in a manner dependent on trophoblast differentiation. (2008)
  • Author(s): Matsumoto J, Kawana K, Nagamatsu T, Schust DJ, Fujii T, Sato H, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Biochem Biophys Res Commun 371 Pages: 236-241
  • Peer Reviewed
• [Journal Article] Prolactin can modulate CD4+ T cell response through receptor-mediated alterations in the expression of T-bet. (2008)
  • Author(s): Tomio A, Schust DJ, Kawana K, Yasugi T, Kawana Y, Mahalingaiah S, Fujii T, Taketani Y
  • Journal Title: Immunol Cell Biol 86 Pages: 616-621
  • Peer Reviewed
• [Journal Article] Cyclic Regulation of T-Bet and GATA-3 in Human Endometrium. (2008)
  • Author(s): Inman DA, Kawana K, Schust DJ, Lininger RA, Young SL
  • Journal Title: Reproductive Sciences 15 Pages: 83-90
  • Peer Reviewed
• [Journal Article] Expression of CD1d and ligand-induced cytokine production are tissue-specific in mucosal epithelia of the human lower reproductive tract. (2008)
  • Author(s): Kawana K, Matsumoto J, Miura S, Shen L, Kawana Y, Nagamatsu T, Yasugi T, Fujii T, Yang H, Quayle AJ, Taketani Y, Schust DJ
  • Journal Title: Infection and Immunity 76 Pages: 3011-3018
  • Peer Reviewed
• [Journal Article] Expression of surface CD1d in the extra-villous trophoblast cells of early gestation placenta is downregulated through TGF-β1 in a manner dependent on trophoblast differentiation. (2008)
  • Author(s): Matsumoto J, Kawana K, Nagamatsu T, Schust DJ, Fujii T, Sato H, Yasugi T, Kozuma S, Taketani Y
  • Journal Title: Biochem Biophys Res Commun, 371 Pages: 236-241
  • Peer Reviewed
• [Journal Article] Prolactin can modulate CD4+ T cell response through receptor-mediated alterations in the expression of T-bet. (2008)
  • Author(s): Tomio A, Schust DJ, Kawana K, Yasugi T, Kawana Y, Mahalingaiah S, Fujii T, Taketani Y
  • Journal Title: Immunol Cell Biol, 86 Pages: 616-621
  • Peer Reviewed
• [Presentation] HPVワクチンの導入とHPV関連癌の予防の可能性～子宮頸癌を中心に～ (2010)
  • Author(s): 川名敬
  • Organizer: 日本エイズ学会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-24
• [Presentation] HPVワクチンの導入とHPV関連癌の予防の可能性～子宮頸癌を中心に～ (2010)
  • Author(s): 川名敬
  • Organizer: 日本エイズ学会、シンポジウム(招待)
  • Place of Presentation: 東京
  • Year and Date: 2010-11-24
• [Presentation] 子宮頸癌前癌病変に対するHPVE7を標的にした癌ワクチン療法の臨床試験における有用性 (2010)
  • Author(s): 川名敬
  • Organizer: 日本癌治療学会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-29
• [Presentation] 子宮頸癌前癌病変に対するHPVE7を標的にした癌ワクチン療法の臨床試験における有用性 (2010)
  • Author(s): 川名敬、小島聡子、横山照史、冨尾賢介、稲葉可奈子、田口歩、塚崎雄大、鶴賀哲史、松本陽子、土谷聡、有本貴英、織田克利、中川俊介、矢野哲、武谷雄二
  • Organizer: 日本癌治療学会、シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2010-10-29
• [Presentation] CIN3に対する乳酸菌HPV治療ワクチン臨床試験例の免疫学的解析 (2010)
  • Author(s): 川名敬
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-23
• [Presentation] CIN3に対する乳酸菌HPV治療ワクチン臨床試験例の免疫学的解析 (2010)
  • Author(s): 川名敬、小島聡子、三浦紫保、足立克之、冨尾文子、冨尾賢介、織田克利、藤井知行、瀬脇智満、上妻志郎、武谷雄二
  • Organizer: 日本産科婦人科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-23
• [Presentation] Oral immunization with Lactobacillus casei vaccine expressing human papillomavirus (HPV) type 16 E7 elicits mucosal cytotoxic cellular immune response to HPV16 E7. (2009)
  • Author(s): Kawana K
  • Organizer: International congress of mucosal immunology
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-07-08
• [Presentation] Oral Immunization with Lactobacillus casei expressing HPV E7 elicits strong mucosal CTL response to HPV16 E7. (2008)
  • Author(s): Kawana K
  • Organizer: Asia Oceania Research Organization on Genital Infections and Neoplasia
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-05-27
• [Presentation] Oral Immunization with Lactobacillus casei ,expressing HPV E7 elicits strong mucosal CTL response to HPV16 E7. (2008)
  • Author(s): Kawana K, Yokoyama T, Yasugi T, Sewaki T, Fujii T, Yano, T, Osanai Y, Taketani Y.
  • Organizer: 3rd Biennial conference of Asia Oceania Research Organization on Genital Infections and Neoplasia
  • Place of Presentation: Seoul
  • Year and Date: 2008-05-27
• [Book] Structure-based study of viral replication, Chapter 19 : Human papillomavirus type 16 capsid proteins : Immunogenicity and possible use as prophylactic vaccine antigens. (2008)
  • Author(s): Kanda T, Kawana K, Yoshikawa H
  • Publisher: World Scientific Publishing Co.
• [Book] Structure-based study of viral replication, (2008)
  • Author(s): Kanda T, Kawana K,. Yoshikawa H
  • Publisher: World Scientific Publishing Co.,
• [Remarks] ホームページ等