Development of a novel vaccine against intracellular bacterial infection by inhibiting immune checkpoint molecules
Project/Area Number |
18H02818
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53030:Respiratory medicine-related
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
Suda Takafumi 浜松医科大学, 医学部, 教授 (30291397)
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Co-Investigator(Kenkyū-buntansha) |
藤澤 朋幸 浜松医科大学, 医学部, 助教 (20402357)
榎本 紀之 浜松医科大学, 医学部附属病院, 講師 (50436961)
中村 祐太郎 浜松医科大学, 医学部附属病院, 講師 (60436962)
永田 年 浜松医科大学, 医学部, 教授 (90275024)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 免疫チェックポイント / ワクチン / 樹状細胞 / PD1/PD-L1 / 細胞内寄生菌 / 免疫チェックポイント分子 / PD-1/PD-L1 / 結核 / 免疫チェックポイント阻害薬 / PD-1/PD-L / 細胞内寄生菌感染症 / 免疫チェックポイント療法 |
Outline of Final Research Achievements |
This study was conducted to develop a powerful cell vaccine against intracellular bacterial infection such as tuberculosis by inhibiting immune check-point molecules that acts as an immune brake. Dendritic cells (BMDCs) cultured from mouse bone marrow strongly express PD-L1, and when mice are inoculated with a cell vaccine in which this BMDC is pulsed with the dominant epitope LLO91-99 of Listeria, administration of anti-PD-1 antibody together induced antigen-specific cytotoxic T cells more efficiently, and enhanced the antigen-specific IFNγ-producing ability. However, in the Listeria monocytogenes-infection model, enhanced protective immunity against Listeria by the administration of anti-PD-1 antibody could not be confirmed.
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Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイン分子を阻害する治療 (ICI) は,生体の免疫を高めて抗腫瘍免疫を増強する新たながんの治療法として,現在,がん治療のパラダイムシフトを起こしている.我々は,全く新たな視点から,このICIを,がんではなく,感染症に対するワクチンの効果を増強する方法として利用することを考えた.そこで,いまだ有効なワクチンのない結核を含む細胞内寄生菌感染症に対して,生体で最も強力な抗原提示細胞である樹状細胞ワクチンを用いて,その効果をICI併用によって高めるICI併用細胞ワクチンの開発に挑んだ.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Conventional type 2 lung dendritic cells are potent inducers of follicular helper T cells in the asthmatic lung2021
Author(s)
Sakurai S, Furuhashi K, Horiguchi R, Nihashi F, Yasui H, Karayama M, Suzuki Y, Hozumi H, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T,
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Journal Title
Allergology International
Volume: -
Issue: 3
Pages: 351-359
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis2021
Author(s)
Sakaue S, Yamaguchi E, Inoue Y, Handa T, Tanizawa K, Ishii H, Ishida M, Kato T, Takeda N, Yokomura K, Matsui T, Watanabe M, Inoue H, Imaizumi K, Goto Y, Kida H, Fujisawa T, Suda T, Yamada T, Satake Y, Ibata H, Hizawa N, Mochizuki H, Kumanogoh A, Matsuda F, Nakata K, Hirota T, Tamari M, Okada Y
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 1032-1032
DOI
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Peer Reviewed / Open Access
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[Journal Article] Ursodeoxycholic acid impairs liver‐infiltrating T‐cell chemotaxis through IFN‐γ and CX3CL1 production in primary biliary cholangitis2021
Author(s)
Shimoyama S, Kawata K, Ohta K, Chida T, Suzuki T, Tsuneyama K, Shimoda S, Kurono N, Leung PSC, Gershwin ME, Suda T, Kobayashi Y
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Journal Title
European Journal of Immunology
Volume: -
Issue: 6
Pages: 1519-1530
DOI
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Peer Reviewed
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[Journal Article] Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium.2020
Author(s)
Kamiya Y, Fujisawa T, Katsumata M, Yasui H, Suzuki Y, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Setou M, Ito M, Suzuki T, Ikegami K, Suda T.
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Journal Title
Respir Res.
Volume: 21
Issue: 1
Pages: 282-282
DOI
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Peer Reviewed / Open Access
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[Journal Article] Evaluation of Programmed Death Ligand 1 (PD-L1) Gene Amplification and Response to Nivolumab Monotherapy in Non-small Cell Lung Cancer2020
Author(s)
Inoue Y, Yoshimura K, Nishimoto K, Inui N, Karayama M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Asada K, Uto T, Fujii M, Matsui T, Matsuura S, Hashimoto D, Toyoshima M, Kusagaya H, Matsuda H, Inami N, Kaida Y, Niwa M, Ito Y, Sugimura H, Suda T.
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Journal Title
JAMA Netw Open.
Volume: 3(9)
Issue: 9
Pages: e2011818-e2011818
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Peer Reviewed / Open Access
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[Journal Article] Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study2020
Author(s)
Suzuki Y, Karayama M, Uto T, Fujii M, Matsui T, Asada K, Kusagaya H, Kato M, Matsuda H, Matsuura S, Toyoshima M, Mori K, Ito Y, Koyauchi T, Yasui H, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T.
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Journal Title
Journal of Thoracic Oncology
Volume: S1556
Issue: 8
Pages: 1317-1327
DOI
Related Report
Peer Reviewed
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[Journal Article] Intravoxel incoherent motion magnetic resonance imaging for predicting the long-term efficacy of immune checkpoint inhibitors in patients with non-small-cell lung cancer.2020
Author(s)
Karayama M, Yoshizawa N, Sugiyama M, Mori K, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Goshima S, Suda T, Takehara Y.
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Journal Title
Lung Cancer
Volume: 143
Pages: 47-54
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-acquired Pneumonia2019
Author(s)
Tsuchiya K, Suzuki Y, Yoshimura K, Yasui H, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Yokomura K, Suda T.
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Journal Title
Sci Rep.
Volume: 9(1)
Issue: 1
Pages: 55289-2
DOI
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Peer Reviewed / Open Access
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[Journal Article] Prognostic factors for primary Sjögren's syndrome-associated interstitial lung diseases.2019
Author(s)
Kamiya Y, Fujisawa T, Kono M, Nakamura H, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Sumikawa H, Johkoh T, Yasui H, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Suda T.
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Journal Title
Respiratory Medicine
Volume: 159
Pages: 105811-105811
DOI
Related Report
Peer Reviewed
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[Journal Article] Effect of PD-1 inhibitor on exhaled nitric oxide and pulmonary function in non-small cell lung cancer patients with and without COPD.2019
Author(s)
Suzuki Y, Inui N, Karayama M, Imokawa S, Yamada T, Yokomura K, Asada K, Kusagaya H, Kaida Y, Matsuda H, Koshimizu N, Toyoshima M, Masuda M, Hayakawa H, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Suda T.
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Journal Title
International Journal of Chronic Obstructive Pulmonary Disease
Volume: 14
Pages: 1867-1877
DOI
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Peer Reviewed / Open Access
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[Journal Article] Clinical significance of serum S100 calcium-binding protein A4 in idiopathic pulmonary fibrosis.2019
Author(s)
Akiyama N, Hozumi H, Isayama T, Okada J, Sugiura K, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T.
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Journal Title
Respirology
Volume: 0
Issue: 7
Pages: 0-0
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Once-daily fluticasone furoate/vilanterol combination versus twice-daily budesonide/formoterol combination in the treatment of controlled stable asthma: a randomized crossover trial.2019
Author(s)
Furuhashi K, Fujisawa T, Hashimoto D, Kamiya Y, Yasui H, Karayama M, Suzuki Y, Hozumi H, Enomoto N, Nakamura Y, Inui N, Suda T.
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Journal Title
Journal of Asthma and Allergy
Volume: 12
Pages: 253-261
DOI
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Peer Reviewed / Open Access
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[Journal Article] Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone.2019
Author(s)
Kono M, Nakamura Y, Enomoto N, Saito G, Koyanagi Y, Miyashita K, Tsutsumi A, Kobayashi T, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Miki Y, Hashimoto D, Fujisawa T, Inui N, Suda T, Nakamura H.
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Journal Title
Respir Investig.
Volume: 57
Issue: 6
Pages: 552-560
DOI
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Peer Reviewed / Open Access
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[Journal Article] Body composition changes successfully classify prognosis in patients with mycobacterium avium complex lung disease.2019
Author(s)
Akahori D, Suzuki Y, Yokomura K, Shirai M, Yasui H, Hozumi H, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Hayakawa H, Suda T.
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Journal Title
Journal of Infection
Volume: 79
Issue: 4
Pages: 341-348
DOI
Related Report
Peer Reviewed
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[Journal Article] Analysis of serum adiponectin and leptin in patients with acute exacerbation of idiopathic pulmonary fibrosis.2019
Author(s)
Enomoto N, Oyama Y, Yasui H, Karayama M, Hozumi H, Suzuki Y, Kono M, Furuhashi K, Fujisawa T, Inui N, Nakamura Y, Suda T.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 10484-10484
DOI
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Peer Reviewed / Open Access
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[Journal Article] Clinical features of three-dimensional computed tomography-based radiologic phenotypes of chronic obstructive pulmonary disease.2019
Author(s)
Karayama M, Inui N, Yasui H, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
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Journal Title
International Journal of Chronic Obstructive Pulmonary Disease
Volume: 14
Pages: 1333-1342
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nationwide cloud-based integrated database of idiopathic interstitial pneumonias for multidisciplinary discussion.2019
Author(s)
Fujisawa T, Mori K, Mikamo M, Ohno T, Kataoka K, Sugimoto C, Kitamura H, Enomoto N, Egashira R, Sumikawa H, Iwasawa T, Matsushita S, Sugiura H, Hashisako M, Tanaka T, Terasaki Y, Kunugi S, Kitani M, Okuda R, Horiike Y, Enomoto Y, Yasui H, Hozumi H, Suzuki Y, Nakamura Y, Fukuoka J, Johkoh T, Kondoh Y, Ogura T,,, Suda T.
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Journal Title
Eur Respir J.
Volume: 3
Issue: 5
Pages: 1802243-1802243
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Development of a Novel T-Cell-Oriented Vaccine, Which Is Composed of Biodegradable Microparticles and T-Cell-Hybrid Epitope Long Peptide, Against Intracellular Bacteria2020
Author(s)
Tanaka K, Enomoto N, Yasui H, Karayama M, Suzuki Y, Hozumi H, Furuhashi K, Fujisawa T, Nakamura Y, Inui N, Nagata T, Suda T
Organizer
American Thoracic Society 2020 International Conference
Related Report
Int'l Joint Research
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[Presentation] Conventional Type 2 Lung Dendritic Cells in Asthma Mouse Model Significantly Induce Follicular Helper T Cells Than Conventional Type 12020
Author(s)
Sakurai S, Furuhashi K, Horiguchi R, Hozumi H, Suzuki Y, Karayama M, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T:
Organizer
American Thoracic Society 2020 International Conference
Related Report
Int'l Joint Research
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[Presentation] Mutlidisciplinary Analysis of Thoracic Lesions in patients with Systemic Lupus Erythematosus: A Retrospective Multicenter Study2018
Author(s)
Enomoto N, Egashira R, Tabata K, Hashisako M, Waseda Y, Ishizuka T, Watanabe S, Kasahara K, Izumi S, Shiraki A, Miyamoto A, Kishi K, Kishaba T, Sugimoto C, Inoue Y, Kataoka K, Kondoh Y, Tsuchiya Y, Baba T, Kitani M, Sugiura H, Tanaka T, Sumikawa H, Suda T
Organizer
American Thoracic Society
Related Report
Int'l Joint Research
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[Presentation] Prognostic Factors in Patients with Chronic Pulmonary Aspergillosis2018
Author(s)
Furuhashi K, Sakurai S, Kamiya Y, Yasui H, Karayama M, Suzuki Y, Hozumi H, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T
Organizer
American Thoracic Society
Related Report
Int'l Joint Research
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[Presentation] Myeloperoxidase-Antineutrophil Cytoplasmic Antibody in Patients with Idiopathic Interstitial Pneumonias2018
Author(s)
Hozumi H, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T
Organizer
American Thoracic Society
Related Report
Int'l Joint Research