Development of novel dendritic -cell vaccine with biodegradable nanoparticles for tuberculosis

• Project/Area Number: 15K09214
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUDA TAKAFUMI 浜松医科大学, 医学部, 教授 (30291397)
• Co-Investigator(Kenkyū-buntansha): 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ワクチン / 樹状細胞 / 結核 / 細胞内寄生菌

Outline of Final Research Achievements

We attempted to develop a novel cell-based vaccine using dendritic cells (DC) and biodegradable polylactic glycolic acid (PLGA)-nanoparticles (PLGA) for intracellular infections, such as tuberculosis. Bone marrow-derived DC pulsed with PLGA, which was coated with ovalbumin protein (OVA) (DC-PLGA/OVA), potently induced a peptide-specific T cell response through efficient cross-presentation in vitro, assessed by peptide-specific T cell proliferation and IFN-gamma production. However, in vivo, immunization with DC-PLGA/OVA failed to elicit a strong peptide-specific T cell response, based on the results of peptide-specific T cell proliferation and the number of peptide-specific T cell determined with tetramer.

Research Products

• [Journal Article] IL-13 regulates IL-17C expression by suppressing NF-κB-mediated transcriptional activation in airway epithelial cells (2018)
  • Author(s): Yamanaka K, Fujisawa T, Kusagaya H, Mori K, Niwa M, Furuhashi K, Kono M, Hamada E, Suda T, Maekawa M.
  • Journal Title: Biochem Biophys Res Commun Volume: 495 Issue: 1 Pages: 1534-1540
  • DOI: 10.1016/j.bbrc.2017.11.207
  • Peer Reviewed / Open Access
• [Journal Article] Podoplanin-positive myofibroblasts: a pathological hallmark of pleuroparenchymal fibroelastosis. (2018)
  • Author(s): Enomoto Y, Matsushima S, Meguro S, Kawasaki H, Kosugi I, Fujisawa T, Enomoto N, Inui N, Nakamura Y, Suda T, Iwashita T.
  • Journal Title: Histopathology. Volume: 印刷中 Issue: 7 Pages: 1209-1215
  • DOI: 10.1111/his.13494
  • Peer Reviewed / Open Access
• [Journal Article] Heterogeneous MET gene copy number and EGFR mutation elicit discordant responses to crizotinib between primary and metastatic lesions in erlotinib-resistant lung adenocarcinoma. (2018)
  • Author(s): Yoshimura K, Karayama M, Inoue Y, Kahyo T, Inui N, Maekawa M, Sugimura H, Suda T
  • Journal Title: Lung Cancer Volume: pii: S0169-5002(18) Pages: 30305-2
  • DOI: 10.1016/j.lungcan.2018.03.016
  • Peer Reviewed / Open Access
• [Journal Article] Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography (2018)
  • Author(s): Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: Clin Exp Allergy Volume: 48 Issue: 3 Pages: 278-287
  • DOI: 10.1111/cea.13083
  • Peer Reviewed
• [Journal Article] Type-1 polarised dendritic cells are a potent immunogen against Mycobacterium tuberculosis (2017)
  • Author(s): Satake Y.、Nakamura Y.、Kono M.、Hozumi H.、Nagata T.、Tsujimura K.、Enomoto N.、Fujisawa T.、Inui N.、Fujiyama T.、Tokura Y.、Matsui T.、Yokomura K.、Shirai M.、Hayakawa H.、Suda T.
  • Journal Title: The International Journal of Tuberculosis and Lung Disease Volume: 21 Issue: 5 Pages: 523-530
  • DOI: 10.5588/ijtld.16.0371
  • Peer Reviewed
• [Journal Article] Critical role of CREBH-mediated induction of transforming growth factor β2 by hepatitis C virus infection in fibrogenic responses in hepatic stellate cells (2017)
  • Author(s): Chida Takeshi、Ito Masahiko、Nakashima Kenji、Kanegae Yumi、Aoshima Takuya、Takabayashi Shuji、Kawata Kazuhito、Nakagawa Yoshimi、Yamamoto Masahiro、Shimano Hitoshi、Matsuura Tomokazu、Kobayashi Yoshimasa、Suda Takafumi、Suzuki Tetsuro
  • Journal Title: Hepatology Volume: 66 Issue: 5 Pages: 1430-1443
  • DOI: 10.1002/hep.29319
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of V-set and immunoglobulin domain containing 1 exerting a tumor suppressor function in gastric, lung, and esophageal cancer cells (2017)
  • Author(s): Inoue Yusuke、Matsuura Shun、Yoshimura Katsuhiro、Iwashita Yuji、Kahyo Tomoaki、Kawase Akikazu、Tanahashi Masayuki、Maeda Matsuyoshi、Ogawa Hiroshi、Inui Naoki、Funai Kazuhito、Shinmura Kazuya、Niwa Hiroshi、Suda Takafumi、Sugimura Haruhiko
  • Journal Title: Cancer Science Volume: 108 Issue: 8 Pages: 1701-1714
  • DOI: 10.1111/cas.13295
  • Peer Reviewed
• [Journal Article] Homeobox Transcription Factor NKX2-1 Promotes Cyclin D1 Transcription in Lung Adenocarcinomas. (2017)
  • Author(s): Harada M, Sakai S, Ohhata T, Kitagawa K, Mikamo M, Nishimoto K, Uchida C, Niida H, Kotake Y, Sugimura H, Suda T, Kitagawa M.
  • Journal Title: Mol Cancer Res. Volume: 15 Issue: 10 Pages: 1388-1397
  • DOI: 10.1158/1541-7786.mcr-17-0114
  • Peer Reviewed
• [Journal Article] Relationship between fraction of exhaled nitric oxide and airway morphology assessed by three-dimensional CT analysis in asthma (2017)
  • Author(s): Nishimoto K, Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 10187-10187
  • DOI: 10.1038/s41598-017-10504-w
  • Peer Reviewed / Open Access
• [Journal Article] Distribution Analysis via Mass Spectrometry Imaging of Ephedrine in the Lungs of Rats Orally Administered the Japanese Kampo Medicine Maoto (2017)
  • Author(s): Matsumoto T, Kushida H, Matsushita S, Oyama Y, Suda T, Watanabe J, Kase Y, Setou M
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 44098-44098
  • DOI: 10.1038/srep44098
  • Peer Reviewed / Open Access
• [Journal Article] Utility of Macrophage-activated Marker CD163 for Diagnosis and Prognosis in Pulmonary Tuberculosis. (2017)
  • Author(s): Suzuki Y, Shirai M, Asada K, Miwa S, Karayama M, Nakamura Y, Inui N, Shirai T, Hayakawa H, Baba S, Suda T
  • Journal Title: Ann Am Thorac Soc Volume: 14 Issue: 1 Pages: 57-64
  • DOI: 10.1513/annalsats.201607-528oc
  • Peer Reviewed
• [Journal Article] Soluble hemoglobin scavenger receptor CD163 (sCD163) predicts mortality of community-acquired pneumonia (2016)
  • Author(s): Suzuki Y, Enomoto Y, Yokomura K, Hozumi H, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T
  • Journal Title: J Infect Volume: 73 Issue: 4 Pages: 375-377
  • DOI: 10.1016/j.jinf.2016.07.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of angiopoietin-1 and -2 on clinical course of idiopathic pulmonary fibrosis (2016)
  • Author(s): Uehara M, Enomoto N, Mikamo M, Oyama Y, Kono M, Fujisawa T, Inui N, Nakamura Y, Suda T
  • Journal Title: Respir Med Volume: 114 Pages: 18-26
  • DOI: 10.1016/j.rmed.2016.03.001
• [Journal Article] Cumulative incidence of tuberculosis in lung cancer patients in Japan: A 6-year observational study (2016)
  • Author(s): Suzuki Y, Imokawa S, Sato J, Uto T, Suda T
  • Journal Title: Respir Investig Volume: 54 Issue: 3 Pages: 179-183
  • DOI: 10.1016/j.resinv.2015.11.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical significance of PDL1 and PDL2 copy number gains in nonsmallcell lung cancer (2016)
  • Author(s): Inoue Y, Yoshimura K, Mori K, Kurabe N, Kahyo T, Mori H, Kawase A, Tanahashi M, Ogawa H, Inui N, Funai K, Shinmura K, Niwa H, Suda T, Sugimura H
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 22 Pages: 32113-32128
  • DOI: 10.18632/oncotarget.8528
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Healthcare-associated pneumonia with positive respiratory methicillin-resistant Staphylococcus aureus culture: Predictors of the true pathogenicity (2016)
  • Author(s): Enomoto Y, Yokomura K, Hasegawa H, Ozawa Y, Matsui T, Suda T
  • Journal Title: Geriatr Gerontol Int Volume: 印刷中 Issue: 3 Pages: 456-462
  • DOI: 10.1111/ggi.12739
  • Peer Reviewed
• [Journal Article] Efficacy of short-term prednisolone treatment in patients with chronic eosinophilic pneumonia (2015)
  • Author(s): Oyama Y, Fujisawa T, Hashimoto D, Enomoto N, Nakamura Y, Inui N, Kuroishi S, Yokomura K, Toyoshima M, Yamada T, Shirai T, Masuda M, Yasuda K, Hayakawa H, Chida K, Suda T
  • Journal Title: Eur Respir J Volume: 45 Issue: 6 Pages: 1624-1631
  • DOI: 10.1183/09031936.00199614
  • Peer Reviewed
• [Journal Article] Synergistic Proinflammatory Responses by IL-17A and Toll-Like Receptor 3 in Human Airway Epithelial Cells (2015)
  • Author(s): Mori K, Fujisawa T, Kusagaya H, Yamanaka K, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Maekawa M, Suda T
  • Journal Title: PLoS One Volume: 10 Issue: 9 Pages: e0139491-e0139491
  • DOI: 10.1371/journal.pone.0139491
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological and Survival Analysis of Japanese Patients with Resected Non-Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA Gene Amplification. (2015)
  • Author(s): Inoue Y, Matsuura S, Kurabe N, Kahyo T, Mori H, Kawase A, Karayama M, Inui N, Funai K, Shinmura K, Suda T, Sugimura H
  • Journal Title: J Thorac Oncol Volume: 10 Issue: 11 Pages: 1590-1600
  • DOI: 10.1097/jto.0000000000000685
  • Peer Reviewed
• [Journal Article] Cumulative Incidence and Predictors of Progression in Corticosteroid-Naive Patients with Sarcoidosis (2015)
  • Author(s): Inoue Y, Inui N, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Suda T
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: e0143371-e0143371
  • DOI: 10.1371/journal.pone.0143371
  • Peer Reviewed / Open Access
• [Journal Article] Nontypeable Haemophilus influenzae exploits the interaction between protein-E and vitronectin for the adherence and invasion to bronchial epithelial cells (2015)
  • Author(s): Ikeda M, Enomoto N, Hashimoto D, Fujisawa T, Inui N, Nakamura Y, Suda T
  • Journal Title: BMC Microbiol Volume: 15 Issue: 1 Pages: 263-263
  • DOI: 10.1186/s12866-015-0600-8
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of antibody levels over 3 years after 23-valent pneumococcal polysaccharide vaccination in patients with pulmonary diseases receiving steroids and immunosuppressive agents. (2015)
  • Author(s): Akamatsu T, Suda T, et al
  • Journal Title: Clin Biochem Volume: 48 Issue: 3 Pages: 125-129
  • DOI: 10.1016/j.clinbiochem.2014.11.005
  • Peer Reviewed / Open Access