Development of Lactobacillus-based therapeutic vaccine against Human papillomavirus for treatment of CIN3 patients
Project/Area Number |
23592436
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | The University of Tokyo |
Principal Investigator |
KAWANA kei 東京大学, 医学部附属病院, 准教授 (60311627)
|
Project Period (FY) |
2011-04-28 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 子宮頸癌 / ヒトパピローマウイルス(HPV) / HPV分子標的がん免疫療法 / 粘膜免疫 / 経口ワクチン / HPV治療ワクチン / 漢方アジュバント / 乳酸菌 / 子宮頚癌前癌病変 / 癌ワクチン / アジュバント / HPV / 乳酸菌ワクチン / E7 / 漢方薬 |
Outline of Final Research Achievements |
Cervicalcancer and its precursor lesion,cervicalintraepithelial neoplasia grade3(CIN3)are a mucosal precancerous lesion caused by high-riskHPV.Induction ofimmunological clearance ofCIN3 by targetingHPV antigens is a strategy for CIN3therapy.We've evaluated the clinical efficacy of an attenuated Lactobacillus casei expressing HPV16E7,GLBL101c,in patients with HPV16-associatedCIN3.GLBL101c had a regression onCIN3to CIN2,but the efficacy remained partial.So we developed next generation E7-expressing Lactobacillus-basedvaccine to improve induction ofmucosalimmune responses to HPVE7. 1)TheJapanese herbalmedicines,JuzenTaihoTo(JTT)/HochuEkkiTo(HET)showed the synergy ofan oralLactobacillus-based vaccine on mucosalimmune responses.2)0.3μgofE7in1.2x10~8cells ofLactobacilluscasei wasthe most effective dose forimmunological inducibility with 2-fold higher thanthe existing,GLBL101c.The optimized newcancer-vaccine with increased pharmacologicaleffect will be a reliable drug for treatmentofCIN2-3.
|
Report
(5 results)
Research Products
(51 results)
-
[Journal Article] Characterization of novel transcripts of human papillomavirus type 16 using CAGE technology2015
Author(s)
Taguchi A, Nagasaka K, Kawana K, Hashimoto K, Kusumoto-Matsuo R, Plessy C, Miranda T, Nakamura H, Bonetti A, Oda K, Kukimoto I, Carninci P, Banks L, Osuga Y, Fujii T,
-
Journal Title
J Virol
Volume: 89
Issue: 4
Pages: 2448-2452
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients2014
Author(s)
Kawana K, Adachi K, Kojima S, Taguchi A, Tomio K, Yamashita A, Nishida H, Nagasaka K, Arimoto T, Yokoyama T, Wada-Hiraike O, Oda K, Sewaki T, Osuga Y, Fujii T
-
Journal Title
Vaccine
Volume: 32
Issue: 47
Pages: 6233-6239
DOI
Related Report
Peer Reviewed
-
[Journal Article] Positive peritoneal cytology at interval debulking surgery is independent poor prognostic factor in patients with stage T3c advanced ovarian carcinoma2014
Author(s)
Nagasaka K, Kawana K, Tomio K, Eguchi S, Miura S, Tsuruga T, Mori-Uchino M, Tanikawa M, Tsukazaki T, Sone K, Adachi K, Matsumoto Y, Arimoto T, Oda K, Osuga Y, Fujii T
-
Journal Title
J Obstet Gynecol Res
Volume: Nov. 25
Issue: 5
Pages: 554-560
DOI
Related Report
Peer Reviewed
-
[Journal Article] Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women2014
Author(s)
Azuma Y, Kusumoto-Matsuo R, Takeuchi F, Uenoyama A, Kondo K, Tsunoda H, Nagasaka K, Kawana K, Morisada T, Iwata T, Aoki D, Kukimoto I
-
Journal Title
Japan J Clin Oncol,
Volume: 44(10)
Issue: 10
Pages: 910-7
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyusaturated fatty acids in vitro and in vivo.2014
Author(s)
Taguchi A, Kawana K, Tomio K, Yamashita A, Isobe Y, Nagasaka K, Koga K, Inoue T, Nishida H, kojima S, Adachi K, Matsumoto Y, Arimoto T, Wada-Hiraike O, Oda K, kang JX, Arai H, Arita M, Osuga Y, Fujii T.
-
Journal Title
PLoS One
Volume: 27
Issue: 2
Pages: e89605-e89605
DOI
Related Report
Peer Reviewed
-
[Journal Article] Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: a possible role of the sirtuin 1 pathway.2014
Author(s)
Taguchi A, Wada-Hiraike O, Kawana K, Koga K, Yamashita A, Shirane A, Urata Y, Kozuma S, Osuga Y, Fujii T,
-
Journal Title
10.1111/jog.12252
Volume: 40
Pages: 770-778
Related Report
Peer Reviewed
-
[Journal Article] High-risk HPV correlates with recurrence after laser ablation for treatment of patients with CIN3: a long-term follow-up retrospective study,2014
Author(s)
Inaba K, Nagasaka K, Kawana K, Arimoto T, Matsumoto Y, Tsuruga T, Mori-Uchino M, Miura S, Sone K, Oda K, Nakagawa S, Yano T, Kozuma S, Fujii T
-
Journal Title
J Obstet Gynaecol Res
Volume: 40
Issue: 2
Pages: 554-60
DOI
Related Report
Peer Reviewed
-
[Journal Article] Anti-tumor activity of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in cultured endometrial carcinoma cells.2014
Author(s)
A. Miyasaka, K. Oda, Y. Ikeda, O. Wada-Hiraike, T. Kashiyama, A. Enomoto, N. Hosoya, T. Koso, T. Fukuda, K. Inaaba, K. Sone, Y. Uehara, R. Kurikawa, K. Nagasaka, Y.Matsumoto, T. Arimoto, S. Nakagawa, H. Kuramoto, K. Miyagawa, T. Yano, K. Kawana, Y. Osuga, T. Fujii.
-
Journal Title
BMC Cancer
Volume: -
Issue: 1
Pages: 179-179
DOI
Related Report
Peer Reviewed
-
[Journal Article] High-risk HPV correlates with recurrence after laser ablation for treatment of patients with CIN3: a long-term follow-up retrospective study,2014
Author(s)
Inaba K, Nagasaka K, Kawana K, Arimoto T, Matsumoto Y, Tsuruga T, Mori-Uchino M, Miura S, Sone K, Oda K, Nakagawa S, Yano T, Kozuma S, Fujii T.
-
Journal Title
The journal of obstetrics and gynaecology research
Volume: 40
Pages: 554-60
Related Report
Peer Reviewed
-
-
-
[Journal Article] A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation2013
Author(s)
Nagasaka K, Seiki T, Yamashita A, Massimi P, Subbaiah VK, Thomas M, Kranjec C, Kawana K, Nakagawa S, Yano T, Taketani Y, Fujii T, Kozuma S, Banks L
-
Journal Title
PLosOne
Volume: E-pub
Issue: 1
Pages: 53752-53760
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Sequential effects of the proteasome inhibitor bortezomib and chemotherapeutic agents in uterine cervical cancer cell lines.2013
Author(s)
Miyamoto Y, Nakagawa S, Wada-Hiraike O, Seiki T, Tanikawa M, Hiraike H, Sone K, Nagasaka K, Oda K, Kawana K, Nakagawa K, Fujii T, Yano T, Kozuma S, Taketani Y.
-
Journal Title
Oncol Rep.
Volume: 29(1)
Issue: 1
Pages: 51-7
DOI
Related Report
Peer Reviewed
-
[Journal Article] The prevalence of cervical regulatory T cells in HPV-related cervical intraepithelial neoplasia (CIN) correlates inversely with spontaneous regression of CIN2013
Author(s)
Kojima S, Kawana K, Tomio K, Yamashita A, Taguchi A, Nagamatsu T, Nagasaka K, Matsumoto Y, Arimoto T, Oda K, Wada-Hiraike O, Yano T, Taketani Y, Fujii T, Schust DJ, Kozuma S
-
Journal Title
Am J Reprod Immunol,
Volume: 69
Issue: 2
Pages: 134-144
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] Association between carotenoids and outcome of cervical intraepithelial neoplasia: a prospective cohort study2013
Author(s)
Fujii T, Takatsuka N, Nagata C, Matsumoto K, Oki A, Furuta R, Maeda H, Yasugi T, Kawana K, Mitsuhashi A, Hirai Y, Iwasaka T, Yaegashi N, Watanabe Y, Nagai Y, Kitagawa T, Yoshikawa H
-
Journal Title
Int J Clin Oncol
Volume: E-pub
Related Report
Peer Reviewed
-
-
-
-
-
[Journal Article] Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas.2012
Author(s)
Shoji K, Oda K, Nakagawa S,-Hiraike O, McCormick F, Aburatani H, Yano T, Kozuma S, Taketani Y.
-
Journal Title
PLoS One
Volume: 7(5):
Issue: 5
Pages: e37431-e37431
DOI
Related Report
Peer Reviewed
-
[Journal Article] Regulation of SIRT1 determines initial step of endometrial receptivity by controlling E-cadherin expression2012
Author(s)
Shirane A, Wada-Hiraike O, Tanikawa M, Seiki T, Hiraike H, Miyamoto Y, Sone K, Hirano M, Oishi H, Oda K, Kawana K, Nakagawa S, Osuga Y, Fujii T, Yano T, Kozuma S, Taketani Y
-
Journal Title
Biochem Biophys Res Commun
Volume: 424
Issue: 3
Pages: 604-10
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] A possible coagulation-independent mechanism for pregnancy 1 loss involving β2glycoprotein 1-dependent antiphospholipid antibodies and CD1d.2012
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
Volume: 67
Pages: 54-65
Related Report
Peer Reviewed
-
-
[Journal Article] Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low-grade cervical lesions?2012
Author(s)
Ochi H, Matsumoto K, Kondo K, Oki A, Furuta R, Hirai Y, Yasugi T, Takatsuka N, Maeda H, Mitsuhashi A, Fujii T, Kawana K, Iwasaka T, Yaegashi N, Watanabe Y, et al
-
Journal Title
J Med Virol
Volume: in-press
Related Report
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,
Volume: 66
Pages: 435-443
Related Report
Peer Reviewed
-
-
-
[Journal Article] Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: Results from a multicenter, prospective, cohort study2011
Author(s)
Matsumoto K, Hirai Y, Furuta R, Takatsuka N, Oki A, Yasugi T, Maeda H, Mitsuhashi A, Fujii T, Kawana K, Iwasaka T, Yaegashi N, Watanabe Y, Nagai Y, Kitagawa T, Yoshikawa H
-
Journal Title
Int J Clin Oncol
Volume: E-pub
NAID
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-