KINDAI UNIVERSITY


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MATSUO Kazuhiko

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FacultyDepartment of Pharmacy
PositionLecturer
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/788-matsuo-kazuhiko.html
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Last Updated :2020/09/30

Education and Career

Academic & Professional Experience

  •   2017 04 ,  - 現在, Faculty of Pharmacy, Department of Pharmacy, Kindai University
  •   2012 04 ,  - 2017 03 , Faculty of Pharmacy, Department of Pharmacy, Kindai University
  •   2011 04 ,  - 2012 03 , Osaka University

Research Activities

Research Areas

  • Life sciences, Infectious disease
  • Life sciences, Clinical pharmacy

Published Papers

  • Epstein-Barr virus-positive pyothorax-associated lymphoma expresses CCL17 and CCL22 chemokines that attract CCR4-expressing regulatory T cells., Higuchi T, Matsuo K, Hashida Y, Kitahata K, Ujihara T, Taniguchi A, Yoshie O, Nakayama T, Daibata M, Cancer letters, Cancer letters, 453, 184 - 192, Jul. 2019 , Refereed
  • Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery., Ito M, Komai K, Mise-Omata S, Iizuka-Koga M, Noguchi Y, Kondo T, Sakai R, Matsuo K, Nakayama T, Yoshie O, Nakatsukasa H, Chikuma S, Shichita T, Yoshimura A, Nature, Nature, 565(7738), 246 - 250, Jan. 2019 , Refereed
  • Vaccination with Antigen Combined with alpha beta-ATP as a Vaccine Adjuvant Enhances Antigen-Specific Antibody Production via Dendritic Cell Activation, Kazuhiko Matsuo, Satoshi Nishiuma, Yuta Hasegawa, Fumika Kawabata, Kosuke Kitahata, Takashi Nakayama, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 39(6), 1073 - 1076, Jun. 2016 , Refereed
    Summary:Adjuvants are required to enhance antigen-specific immune responses by vaccines. Extracellular ATP serves as a danger signal to alert the immune system of tissue damage by acting on P2X and P2Y receptors and triggers the activation of dendritic cells (DCs). Here we investigated the in vivo adjuvant efficacy of alpha,beta-methylene-ATP (alpha beta-ATP), a non-hydrolysable form of ATP. We found that intradermal injection of ovalbumin (OVA), as a model antigen, combined with alpha beta-ATP, as the adjuvant, enhanced OVA-specific immune responses more than OVA alone. Additionally, DCs in the skin of mice injected with OVA and alpha beta-ATP had increased expression of major histocompatibility complex class II and co-stimulator molecules, CD40, CD80, and CD86, suggesting that alpha beta-ATP activated DC. These findings indicate that alpha beta-ATP functions as a potent vaccine adjuvant.
  • Vaccine efficacy of transcutaneous immunization with amyloid beta using a dissolving microneedle array in a mouse model of Alzheimer's disease, Kazuhiko Matsuo, Hideaki Okamoto, Yasuaki Kawai, Ying-Shu Quan, Fumio Kamiyama, Sachiko Hirobe, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF NEUROIMMUNOLOGY, JOURNAL OF NEUROIMMUNOLOGY, 266(1-2), 1 - 11, Jan. 2014 , Refereed
    Summary:Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treating AD. Injectable immunization using amyloid r3 peptide (A beta) comprising 1-42 amino-acid residues (A beta 1-42) as antigens showed therapeutic efficacy in mice; however, the clinical trial of this injected A beta 1-42 vaccine was stopped due to the incidence of meningoencephalitis caused by excess activation of Th1 cells infiltrating the brain as a serious adverse reaction. Because recent studies have suggested that transcutaneous immunization (TCI) is likely to elicit Th2-dominant immune responses, TCI is expected to be effective in treating AD without inducing adverse reactions. Previously reported TCI procedures employed complicated and impractical vaccination procedures; therefore, a simple, easy-to-use, and novel TCI approach needs to be established. In this study, we investigated the vaccine efficacy of an A beta 1-42-containing TCI using our novel dissolving microneedle array (MicroHyala; MH) against AD. MH-based TCI induced anti-A beta 1-42 immune responses by simple and low-invasive application of A beta 1-42-containing MH to the skin. Unfortunately, this TCI system resulted in little significant improvement in cognitive function and Th2-dominant immune responses, suggesting the need for further modification. (c) 2013 Elsevier B.V. All rights reserved.
  • Induction of Endoplasmic Reticulum-Endosome Fusion for Antigen Cross-Presentation Induced by Poly (gamma-Glutamic Acid) Nanoparticles, Yohei Mukai, Tomoyo Yoshinaga, Mai Yoshikawa, Kazuhiko Matsuo, Tomoaki Yoshikawa, Keisuke Matsuo, Kazuyuki Niki, Yasuo Yoshioka, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF IMMUNOLOGY, JOURNAL OF IMMUNOLOGY, 187(12), 6249 - 6255, Dec. 2011 , Refereed
    Summary:We previously reported that poly (gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers for inducing efficient cross-presentation in dendritic cells, thereby producing strong antitumor immunity in vivo. Analyzing the mechanism of cross-presentation induced by gamma-PGA NPs will be useful toward designing novel vaccine carriers. In this study, we show an intracellular mechanism of efficient cross-presentation induced by OVA-loaded gamma-PGA NPs. Cross-presentation induced by gamma-PGA NPs depended on cytoplasmic proteasomes and TAP, similar to the classical MHC class I presentation pathway for endogenous Ags. Intracellular behavior analyzed by confocal laser scanning microscopy revealed that encapsulated OVA and gamma-PGA accumulated in both the endoplasmic reticulum (ER) and endosome compartments within 2 h. At the same time, electron microscopy analysis clearly showed that intracellular gamma-PGA NPs and encapsulated Au NPs were enveloped in endosome-like vesicles, not in the ER. These findings strongly suggest that gamma-PGA NPs enhance ER-endosome fusion for cross-presentation. Moreover, inhibition of ER translocon sec61 significantly decreased the gamma-PGA NP/OVA-mediated cross-presentation efficiency, indicating that sec61 is important for transporting Ags from the fused ER-endosome to the cytoplasm. These findings imply that the ER-endosome complex is key for the efficient cross-presentation of Ags encapsulated in gamma-PGA NPs. The Journal of Immunology, 2011, 187: 6249-6255.
  • The Utility of Poly(gamma-glutamic acid) Nanoparticles as Antigen Delivery Carriers in Dendritic Cell-Based Cancer Immunotherapy, Keisuke Matsuo, Yumiko Ishii, Kazuhiko Matsuo, Tomoyo Yoshinaga, Mitsuru Akashi, Yohei Mukai, Yasuo Yoshioka, Naoki Okada, Shinsaku Nakagawa, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 33(12), 2003 - 2007, Dec. 2010 , Refereed
    Summary:Cytotoxic T-lymphocytes (CTLs) specific for tumor-associated antigens (TAAs) act in the immune surveillance system as major effector cells to eliminate malignant cells Immunization with TAA-loaded dendritic cells (DCs) has great potential for treating cancer, because DCs are potent antigen-presenting cells capable of inducing antigen-specific CTLs by the primary activation of naive T-lymphocytes The establishment of a non-cyto-toxic and efficient antigen delivery method is required to Improve the efficacy of DC-based cancer immunotherapy We developed biodegradable poly(gamma-glutamic acid) nanoparticles (gamma-PGA NPs) that can efficiently entrap various proteins as antigen delivery carriers gamma-PGA NPs efficiently delivered entrapped antigenic proteins into DCs without cytotoxicity and presented antigens to DCs via major histocompatibility complex class I and II molecules Immunization with TAA-loaded DCs using gamma-PGA NPs inhibited tumor growth by inducing TAA-specific CTLs These findings indicate that gamma-PGA NPs can function as useful antigen delivery carriers in DC-based cancer Immunotherapy
  • Transcutaneous immunization with a highly active form of XCL1 as a vaccine adjuvant using a hydrophilic gel patch elicits long-term CD8+ T cell responses, Momo Kamei, Kazuhiko Matsuo, Haruka Imanishi, Yuta Hara, Ying-Shu Quen, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Naoki Okada, Takashi Nakayama, J. Pharmacol. Sci., J. Pharmacol. Sci., 143(3), 182 - 187, Jul. 2020 , Refereed
  • Interstitial-resident memory CD8+ T cells sustain frontline epithelial memory in the lung., Shiki Takamura, Shigeki Kato, Chihiro Motozono, Takeshi Shimaoka, Satoshi Ueha, Kazuhiko Matsuo, Kosuke Miyauchi, Tomoko Masumoto, Asami Katsushima, Takashi Nakayama, Michio Tomura, Kouji Matsushima, Masato Kubo, Masaaki Miyazawa, The Journal of experimental medicine, The Journal of experimental medicine, 216(12), 2736 - 2747, Dec. 02 2019 , Refereed
    Summary:Populations of CD8+ lung-resident memory T (TRM) cells persist in the interstitium and epithelium (airways) following recovery from respiratory virus infections. While it is clear that CD8+ TRM cells in the airways are dynamically maintained via the continuous recruitment of new cells, there is a vigorous debate about whether tissue-circulating effector memory T (TEM) cells are the source of these newly recruited cells. Here we definitively demonstrate that CD8+ TRM cells in the lung airways are not derived from TEM cells in the circulation, but are seeded continuously by TRM cells from the lung interstitium. This process is driven by CXCR6 that is expressed uniquely on TRM cells but not TEM cells. We further demonstrate that the lung interstitium CD8+ TRM cell population is also maintained independently of TEM cells via a homeostatic proliferation mechanism. Taken together, these data show that lung memory CD8+ TRM cells in the lung interstitium and airways are compartmentally separated from TEM cells and clarify the mechanisms underlying their maintenance.
  • A CCR4 antagonist ameliorates atopic dermatitis-like skin lesions induced by dibutyl phthalate and a hydrogel patch containing ovalbumin., Kazuhiko Matsuo, Shota Hatanaka, Yuta Kimura, Yuta Hara, Keiji Nishiwaki, Ying-Shu Quan, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Kenji Kabashima, Takashi Nakayama, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 109, 1437 - 1444, Jan. 2019 , Refereed
    Summary:CCR4 is a chemokine receptor highly expressed by Th2 cells, and regarded as a potential therapeutic target for atopic dermatitis (AD). CCL17 and CCL22 are the CCR4 ligands, and thymic stromal lymphopoietin (TSLP) is shown to promote the expression of CCL17 and CCL22 by dendritic cells. Here, by using dibutyl phthalate (DBP), a TSLP inducer, and a hydrogel patch as a transcutaneous delivery device for ovalbumin, we developed a novel murine AD model and investigated the effect of Compound 22, a CCR4 antagonist. We first found that the mRNA expression of TSLP together with CCL17 and CCL22 was increased in the skins treated with DBP. Furthermore, the topical application of ovalbumin and DBP efficiently and rapidly induced AD-like skin lesions in BALB/c mice, which were characterized by ear swelling accompanied by infiltration of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions, and elevated total IgE levels in the sera. Using this AD model, we demonstrated that cutaneous administration of Compound 22 inhibited Th2 cell infiltration and ameliorated the AD-like skin lesions. These results suggest that our AD model could be useful for studying new therapeutic strategies. Collectively, CCR4 antagonists may be a promising approach for treating AD.
  • Ascorbic acid derivative DDH-1 ameliorates psoriasis-like skin lesions in mice by suppressing inflammatory cytokine expression., Kosuke Kitahata, Kazuhiko Matsuo, Yuta Hara, Takanori Naganuma, Naoki Oiso, Akira Kawada, Takashi Nakayama, Journal of pharmacological sciences, Journal of pharmacological sciences, 138(4), 284 - 288, Dec. 2018 , Refereed
    Summary:Psoriasis is a chronic inflammatory skin disease in which inflammatory cytokines play a major role in its pathogenesis. Because DDH-1, a novel amphipathic ascorbic acid derivative, has been recently shown to reduce inflammatory cytokine expression in human keratinocytes in vitro, we investigated its effect on imiquimod-induced psoriasis-like skin lesions in C57BL/6 mice. We first found that IL-1β and TNF-α mRNA expression was significantly decreased in the skin lesions treated with DDH-1. Furthermore, cutaneous administration of DDH-1 ameliorated psoriasis-like skin lesions. These results suggest that DDH-1 may be effective in the prevention and supplemental treatment of psoriasis.
  • CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice., Kazuhiko Matsuo, Daisuke Nagakubo, Yuhei Komori, Shun Fujisato, Natsumi Takeda, Mizuki Kitamatsu, Keiji Nishiwaki, Ying-Shu Quan, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama, The Journal of investigative dermatology, The Journal of investigative dermatology, 138(8), 1764 - 1773, Aug. 2018 , Refereed
    Summary:Atopic dermatitis is a chronic inflammatory skin disease involving T-helper (Th) 2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in atopic dermatitis remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute atopic dermatitis-like skin lesions in BALB/c mice, a strain prone to Th2 responses, which were characterized by increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions; elevated levels of total and ovalbumin-specific IgE in the sera; and increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions. Of note, the same model was less efficient in C57BL/6 mice, a strain prone to Th1 responses. Using this atopic dermatitis model in BALB/c mice, we demonstrated that CCR4-deficiency or a CCR4 antagonist ameliorated the allergic responses. Collectively, these results demonstrate that CCR4 plays a pivotal role in skin allergic inflammation of BALB/c mice by recruiting CCR4-expressing Th2 cells and Th17 cells.
  • A CCR4 antagonist enhances DC activation and homing to the regional lymph node and shows potent vaccine adjuvant activity through the inhibition of regulatory T-cell recruitment., Shinya Yamamoto, Kazuhiko Matsuo, Daisuke Nagakubo, Shintaro Higashiyama, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama, Journal of pharmacological sciences, Journal of pharmacological sciences, 136(3), 165 - 171, Mar. 2018 , Refereed
    Summary:CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice. Furthermore, OVA-loaded dendritic cells (DCs) derived from the muscle injection site of CCR4-deficient mice had an upregulated expression of the DC activation marker CD40 and 86, and the lymphoid organ homing receptor CCR7 resulting in an increased number of migratory DCs in the regional lymph node. Compound 22, a CCR4 antagonist, also inhibited the recruitment of Treg cells to the muscle tissue, and further enhanced DC activation and homing to the regional lymph node. Consequently, Compound 22 enhanced OVA-specific IgG responses, and the expression levels of IL-4 and IFN-γ in CD4+ T cells and the levels of IFN-γ in CD8+ T cells. Finally, intramuscular administration of OVA and Compound 22 significantly inhibited the growth of OVA-expressing tumors. Collectively, CCR4 plays a pivotal role in Treg cell recruitment to the muscle tissue, and intramuscular administration of CCR4 antagonists may be a promising approach for enhancing vaccine efficacy.
  • CCL28-Deficient Mice Have Reduced IgA Antibody-Secreting Cells and an Altered Microbiota in the Colon., Kazuhiko Matsuo, Daisuke Nagakubo, Shinya Yamamoto, Akiko Shigeta, Shuta Tomida, Mitsugu Fujita, Takako Hirata, Ikuo Tsunoda, Takashi Nakayama, Osamu Yoshie, Journal of immunology (Baltimore, Md. : 1950), Journal of immunology (Baltimore, Md. : 1950), 200(2), 800 - 809, Jan. 15 2018 , Refereed
    Summary:CCL28 induces the migration of IgA Ab-secreting cells (ASCs) via CCR10 and also displays a potent antimicrobial activity in vitro. To explore the role of CCL28 in vivo, we generated CCL28-deficient mice. The mice exhibited a significant reduction and abnormal distribution of IgA ASCs in the lamina propria of the colon. The concentrations of total and Ag-specific IgA in the fecal extracts of CCL28-deficient mice were also drastically reduced. The average amount of IgA secreted by a single IgA ASC derived from the colon was also substantially reduced in CCL28-deficient mice. Furthermore, CCL28 was found to significantly increase the average amount of IgA secreted by a single IgA ASC derived from the colon in vitro. In contrast, the generation of IgA ASCs in Peyer's and cecal patches was not significantly impaired in CCL28-deficient mice. We also found a relative increase in the Class Bacilli in the fecal extracts of CCL28-deficient mice and demonstrated a potent antimicrobial activity of CCL28 against Bacillus cereus and Enterococcus faecalis, both of which belong to Class Bacilli. Thus, CCL28 may also suppress the outgrowth of some bacterial species by its direct antimicrobial activity. Finally, CCL28-deficient mice exhibited a highly aggravated dextran sodium sulfate-induced colitis that was ameliorated by pretreatment with antibiotics. Collectively, CCL28 plays a pivotal role in the homing, distribution, and function of IgA ASCs in the colon and may also affect the intestinal microbiota through its direct antimicrobial activity.
  • A Highly Active Form of XCL1/Lymphotactin Functions as an Effective Adjuvant to Recruit Cross-Presenting Dendritic Cells for Induction of Effector and Memory CD8+ T Cells., Kazuhiko Matsuo, Kosuke Kitahata, Fumika Kawabata, Momo Kamei, Yuta Hara, Shiki Takamura, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama, Frontiers in immunology, Frontiers in immunology, 9, 2775 - 2775, 2018 , Refereed
    Summary:The chemokine receptor XCR1 is known to be selectively expressed by cross-presenting dendritic cells (DCs), while its ligand XCL1/lymphotactin is mainly produced by activated CD8+ T cells and natural killer cells. Recent studies have shown that XCL1-antigen fusion proteins efficiently induce CD8+ T cell responses by preferentially delivering antigens to XCR1+ DCs. However, XCL1 per se was found to be a poor adjuvant for induction of CD8+ T cell responses. XCL1 is unique because of its lack of one of the two disulfide bonds commonly conserved in all other chemokines and thus has an unstable structure with a relatively weak chemokine activity. In the present study, we generated a variant form of murine XCL1 termed mXCL1-V21C/A59C that contained a second disulfide bond to stabilize its chemokine structure. We confirmed that mXCL1-V21C/A59C had much more potent chemotactic and calcium mobilization activities than the wild type XCL1 (mXCL1-WT). Intradermal injection of mXCL1-V21C/A59C, but not that of mXCL1-WT, significantly increased the accumulation of XCR1+CD103+ DCs in the injection site, and most of the accumulated XCR1+CD103+ DCs were found to take up co-injected ovalbumin (OVA). Furthermore, recruited XCR1+CD103+ DCs efficiently migrated to the draining lymph nodes and stayed for a prolonged period of time. Consequently, mXCL1-V21C/A59C strongly induced OVA-specific CD8+ T cells. The combination of OVA and mXCL1-V21C/A59C well protected mice from E.G7-OVA tumor growth in both prophylactic and therapeutic protocols. Finally, memory CTL responses were efficiently induced in mice immunized with OVA and mXCL1-V21C/A59C. Although intradermal injection of OVA and polyinosinic-polycytidylic acid (poly(I:C)) as an adjuvant also induced CD8+ T cell responses to OVA, poly (I:C) poorly recruited XCR1+CD103+ DCs in the injection site and failed to induce significant memory CTL responses to OVA. Collectively, our findings demonstrate that a highly active form of XCL1 is a promising vaccine adjuvant for cross-presenting DCs to induce antigen-specific effector and memory CD8+ T cells.
  • Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1, Rana Mashud, Akira Nomachi, Akihide Hayakawa, Koji Kubouchi, Sally Danno, Takako Hirata, Kazuhiko Matsuo, Takashi Nakayama, Ryosuke Satoh, Reiko Sugiura, Manabu Abe, Kenji Sakimura, Shigeharu Wakana, Hiroyuki Ohsaki, Shingo Kamoshida, Hideyuki Mukai, SCIENTIFIC REPORTS, SCIENTIFIC REPORTS, 7(1), 7663, Aug. 2017 , Refereed
    Summary:Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those of wild-type (WT) mice. T and B cell development proceeded in an apparently normal fashion in bone marrow and thymus of PKN1[T778A] mice, however, the number of T and B cell counts were significantly higher in the lymph nodes and spleen of mutant mice in those of WT mice. After transfusion into WT recipients, EGFP-labelled PKN1[T778A] donor lymphocytes were significantly less abundant in the peripheral circulation and more abundant in the spleen and lymph nodes of recipient mice compared with EGFP-labelled WT donor lymphocytes, likely reflecting lymphocyte sequestration in the spleen and lymph nodes in a cell-autonomous fashion. PKN1[T778A] lymphocytes showed significantly lower chemotaxis towards chemokines and sphingosine 1-phosphate (S1P) than WT cells in vitro. The biggest migration defect was observed in response to S1P, which is essential for lymphocyte egress from secondary lymphoid organs. These results reveal a novel role of PKN1 in lymphocyte migration and localization.
  • CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma., Kazuhiko Matsuo, Tatsuki Itoh, Atsushi Koyama, Reira Imamura, Shiori Kawai, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama, Cancer letters, Cancer letters, 378(1), 16 - 22, Aug. 01 2016 , Refereed
    Summary:CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma.
  • Neolignans from the Arils of Myristica fragrans as Potent Antagonists of CC Chemokine Receptor 3, Toshio Morikawa, Ikuko Hachiman, Kazuhiko Matsuo, Eriko Nishida, Kiyofumi Ninomiya, Takao Hayakawa, Osamu Yoshie, Osamu Muraoka, Takashi Nakayama, JOURNAL OF NATURAL PRODUCTS, JOURNAL OF NATURAL PRODUCTS, 79(8), 2005 - 2013, Aug. 2016 , Refereed
    Summary:CC chemokine receptor 3 (CCR3) is expressed selectively in eosinophils, basophils, and some Th2 cells and plays a major role in allergic diseases. A methanol extract from the arils of Myristica fragrans inhibited CC chemokine ligand 11-induced chemotaxis in CCR3-expressing L1.2 cells at 100 mu g/mL. From this extract, eight new neolignans, maceneolignans A-H (1-8), were isolated, and their stereostructures were elucidated from their spectroscopic values and chemical properties. Of those constituents, compounds 1, 4, 6, and 8 and (+)-erythro-(7S,8R)-Delta(8)'-7-hydroxy-3,4-methylenedioxy-3,5'-dimethoxy-8-O-4'-neolignan (11), (-)- (8R)-Delta(8,)-3,4-methylene dioxy-3',5-dimethoxy-8-O-4'-neolignan (17), (+)-licarin A (20), nectandrin B (25), verrucosin (26), and myristicin (27) inhibited CCR3-mediated chemotaxis at, a concentration of 1 mu M. Among them, 1 (EC50 1.6 mu M), 6 (1.5 mu M), and 8 (1.4 mu M) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 mu M).
  • Analysis of Skin Permeability and Toxicological Properties of Amorphous Silica Particles, Kazuhiko Matsuo, Sachiko Hirobe, Naoki Okada, Shinsaku Nakagawa, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 39(7), 1201 - 1205, Jul. 2016 , Refereed
    Summary:Nanomaterials (NMs) are defined as those which have nanostructured components less than 100 nm in diameter. They are widely used in various fields such as medicine, cosmetics, and the food industry. However, the toxicological effects of NMs are less well understood than their applications. In particular, the skin is exposed to the environment at all times, so is easily influenced by NMs. In this study, we investigated the skin permeability and toxicological properties of well-dispersed amorphous silica particles with diameters ranging from 70 to 1000 nm, to aid in the safe application of NMs. Amorphous silica particles of 70 nm in size (nSP70) penetrated the living epidermis, following pretreatment with acetone/diethyl ether to improve skin permeation. The application of unmodified nSP70, carboxyl group-modified nSP70, or amino group-modified nSP70 for long durations caused little skin irritation at the application site. Under the present experimental conditions, few adverse systemic effects were evident from blood tests and histopathologic examination. These results suggest that decreasing particle size increases the NMs skin permeability, but remarkably little corresponding skin irritation is observed.
  • Efficient Use of a Crude Drug/Herb Library Reveals Ephedra Herb As a Specific Antagonist for TH2-Specific Chemokine Receptors CCR3, CCR4, and CCR8., Kazuhiko Matsuo, Keiichi Koizumi, Mitsugu Fujita, Toshio Morikawa, Michiko Jo, Naotoshi Shibahara, Ikuo Saiki, Osamu Yoshie, Takashi Nakayama, Frontiers in cell and developmental biology, Frontiers in cell and developmental biology, 4, 54 - 54, 2016 , Refereed
    Summary:Chemokine receptors CCR3 and CCR4 are preferentially expressed by TH2 cells, mast cells, and/or eosinophils, all of which are involved in the pathogenesis of allergic diseases. Therefore, CCR3 and CCR4 have long been highlighted as potent therapeutic targets for allergic diseases. Japanese traditional herbal medicine Kampo consists of multiple crude drugs/herbs, which further consist of numerous chemical substances. Recent studies have demonstrated that such chemical substances appear to promising sources in the development of novel therapeutic agents. Based on these findings, we hypothesize that Kampo-related crude drugs/herbs would contain chemical substances that inhibit the cell migration mediated by CCR3 and/or CCR4. To test this hypothesis, we screened 80 crude drugs/herbs to identify candidate substances using chemotaxis assay. Among those tested, Ephedra Herb inhibited the chemotaxis mediated by both CCR3 and CCR4, Cornus Fruit inhibited that mediated by CCR3, and Rhubarb inhibited that mediated by CCR4. Furthermore, Ephedra Herb specifically inhibited the chemotaxis mediated by not only CCR3 and CCR4 but CCR8, all of which are selectively expressed by TH2 cells. This result led us to speculate that ephedrine, a major component of Ephedra Herb, would play a central role in the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8. However, ephedrine exhibited little effects on the chemotaxis. Therefore, we fractionated Ephedra Herb into four subfractions and examined the inhibitory effects of each subfraction. As the results, ethyl acetate-insoluble fraction exhibited the inhibitory effects on chemotaxis and calcium mobilization mediated by CCR3 and CCR4 most significantly. In contrast, chloroform-soluble fraction exhibited a weak inhibitory effect on the chemotaxis mediated by CCR8. Furthermore, maoto, one of the Kampo formulations containing Ephedra Herb, exhibited the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8. Taken together, our data suggest that these crude drugs/herbs might be useful sources to develop new drugs targeting TH2-mediated allergic diseases.
  • Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch, Sachiko Hirobe, Hiroaki Azukizawa, Takaaki Hanafusa, Kazuhiko Matsuo, Ying-Shu Quan, Fumio Kamiyama, Ichiro Katayama, Naoki Okada, Shinsaku Nakagawa, BIOMATERIALS, BIOMATERIALS, 57, 50 - 58, Jul. 2015 , Refereed
    Summary:Transcutaneous immunization (TCI) is an attractive vaccination method compared with conventional injectable vaccines because it is easier to administer without pain. We developed a dissolving microneedle patch (MicroHyala, MH) made of hyaluronic acid and showed that transcutaneous vaccination using MH induced a strong immune response against various antigens in mice. In the present study, we investigated the clinical safety and efficacy of a novel transcutaneous influenza vaccine using MH (flu-MH), which contains trivalent influenza hemagglutinins (15 mu g each). Subjects of the TCI group were treated transcutaneously with flu-MH, and were compared with subjects who received subcutaneous injections of a solution containing 15 mu g of each influenza antigen (SCI group). No severe local or systemic adverse events were detected in either group and immune responses against A/H1N1 and A/H3N2 strains were induced equally in the TCI and SCI groups. Moreover, the efficacy of the vaccine against the B strain in the TCI group was stronger than that in the SCI group. Influenza vaccination using MH is promising for practical use as an easy and effective method to replace conventional injections systems. (C) 2015 Elsevier Ltd. All rights reserved.
  • Erratum: A low-invasive and effective transcutaneous immunization system using a novel dissolving microneedle array for soluble and particulate antigens (Journal of Controlled Release (2012) 161 (10-17)), Kazuhiko Matsuo, Yayoi Yokota, You Zhai, Ying-Shu Quan, Fumio Kamiyama, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, Journal of Controlled Release, Journal of Controlled Release, 184(1), 9, Jun. 28 2014 , Refereed
  • Necrobiosis lipoidica with infiltration of Th17 cells into vascular lesions, Maiko Kato, Naoki Oiso, Tatsuki Itoh, Masako Sato, Kazuhiko Matsuo, Takashi Nakayama, Takao Satou, Akira Kawada, JOURNAL OF DERMATOLOGY, JOURNAL OF DERMATOLOGY, 41(5), 459 - 461, May 2014 , Refereed
  • Development and Clinical Study of a Self-Dissolving Microneedle Patch for Transcutaneous Immunization Device, Sachiko Hirobe, Hiroaki Azukizawa, Kazuhiko Matsuo, You Zhai, Ying-Shu Quan, Fumio Kamiyama, Hiroshi Suzuki, Ichiro Katayama, Naoki Okada, Shinsaku Nakagawa, PHARMACEUTICAL RESEARCH, PHARMACEUTICAL RESEARCH, 30(10), 2664 - 2674, Oct. 2013 , Refereed
    Summary:We previously reported the safety and efficacy in animal experiments of transcutaneous immunization (TCI) using a self-dissolving microneedle patch (MicroHyala; MH) made of hyaluronic acid and collagen. However, this MH was an unsuitable TCI device for the human skin, as collagen is suspected to induce inflammation. In this study, we developed an improved collagen-free MH (new-MH) and conducted clinical study to evaluate the fundamental properties and safety in human.Microneedle dissolution, skin irritation, and antigen-specific antibody production about new-MH were measured in mice and/or rats. On the basis of the results, the clinical study was conducted in healthy volunteers to evaluate local and systemic adverse events caused by new-MH application.We confirmed that the microneedles of new-MH, as well as those on our old-MH that contained collagen, could easily pierce stratum corneum without severe skin irritation, and that TCI using new-MH efficiently increased antibody titer with comparable to TCI using old-MH. Application of new-MH caused no severe adverse reactions in 20 healthy volunteers enrolled in a clinical study.These results verified that new-MH is a safe TCI device in human, and greatly encouraged us to advance PI/PII clinical studies of antigen-loaded new-MH.
  • Neuroprotective effect of (-)-epigallocatechin-3-gallate in rats when administered pre- or post-traumatic brain injury, Tatsuki Itoh, Masaki Tabuchi, Nobuyuki Mizuguchi, Motohiro Imano, Masahiro Tsubaki, Shozo Nishida, Shigeo Hashimoto, Kazuhiko Matsuo, Takashi Nakayama, Akihiko Ito, Hiroshi Munakata, Takao Satou, JOURNAL OF NEURAL TRANSMISSION, JOURNAL OF NEURAL TRANSMISSION, 120(5), 767 - 783, May 2013 , Refereed
    Summary:Our previous study indicated that consuming (-)-epigallocatechin gallate (EGCG) before or after traumatic brain injury (TBI) eliminated free radical generation in rats, resulting in inhibition of neuronal degeneration and apoptotic death, and improvement of cognitive impairment. Here we investigated the effects of administering EGCG at various times pre- and post-TBI on cerebral function and morphology. Wistar rats were divided into five groups and were allowed access to (1) normal drinking water, (2) EGCG pre-TBI, (3) EGCG pre- and post-TBI, (4) EGCG post-TBI, and (5) sham-operated group with access to normal drinking water. TBI was induced with a pneumatic controlled injury device at 10 weeks of age. Immunohistochemistry and lipid peroxidation studies revealed that at 1, 3, and 7 days post-TBI, the number of 8-Hydroxy-2'-deoxyguanosine-, 4-Hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and levels of malondialdehyde around the damaged area were significantly decreased in all EGCG treatment groups compared with the water group (P < 0.05). Although there was a significant increase in the number of surviving neurons after TBI in each EGCG treatment group compared with the water group (P < 0.05), significant improvement of cognitive impairment after TBI was only observed in the groups with continuous and post-TBI access to EGCG (P < 0.05). These results indicate that EGCG inhibits free radical-induced neuronal degeneration and apoptotic death around the area damaged by TBI. Importantly, continuous and post-TBI access to EGCG improved cerebral function following TBI. In summary, consumption of green tea may be an effective therapy for TBI patients.
  • Frontiers of transcutaneous vaccination systems: Novel technologies and devices for vaccine delivery, Kazuhiko Matsuo, Sachiko Hirobe, Naoki Okada, Shinsaku Nakagawa, Vaccine, Vaccine, 31(19), 2403 - 2415, May 01 2013 , Refereed
    Summary:Transcutaneous immunization (TCI) systems that use the skin's immune function are promising needle-free, easy-to-use, and low-invasive vaccination alternative to conventional, injectable vaccination methods. To develop effective TCI systems, it is essential to establish fundamental techniques and technologies that deliver antigenic proteins to antigen-presenting cells in the epidermis and dermis while overcoming the barrier function of the stratum corneum. In this review, we provide an outline of recent trends in the development of techniques for the delivery of antigenic proteins and of the technologies used to enhance TCI systems. We also introduce basic and clinical research involving our TCI systems that incorporate several original devices. © 2013 Elsevier Ltd.
  • Analysis of transcutaneous antigenic protein delivery by a hydrogel patch formulation, Kazuhiko Matsuo, Yumiko Ishii, Yasuaki Kawai, Yuki Saiba, Ying-Shu Quan, Fumio Kamiyama, Sachiko Hirobe, Naoki Okada, Shinsaku Nakagawa, Journal of Pharmaceutical Sciences, Journal of Pharmaceutical Sciences, 102(6), 1936 - 1947, 2013 , Refereed
    Summary:We have developed a hydrogel patch, which could promote antigen penetration through stratum corneum (SC), and have demonstrated its safety and efficacy in animals and humans. For the availability improvement of our system, it is important to develop a device, which enhances antigen penetration through SC more efficiently. In this study, we have tried to collect the basic information involved in transcutaneous antigen delivery by investigating the immune event induced by our system and examining the effect of physical property of antigens or patch component on antigen penetration. A hydrogel patch delivered antigens through SC into skin, and some of Langerhans cells captured antigens, activated, and migrated to regional lymph nodes. We also showed that protein distribution into SC was regulated by various complexly-intertwined factors of proteins but not one particular parameter. Additionally, glycerin as the patch component contributed to the formation of SC hydration by patch application, which might be one of the factors of acceleration of protein penetration. On the basis of the present information, we are planning to modify the patch composition and establish the antigen modification technology for improvement in the efficacy of transcutaneous immunization. © 2013 Wiley Periodicals, Inc.
  • A low-invasive and effective transcutaneous immunization system using a novel dissolving microneedle array for soluble and particulate antigens, Kazuhiko Matsuo, Yayoi Yokota, You Zhai, Ying-Shu Quan, Fumio Kamiyama, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF CONTROLLED RELEASE, JOURNAL OF CONTROLLED RELEASE, 161(1), 10 - 17, Jul. 2012 , Refereed
    Summary:Transcutaneous immunization (TCI) is a promising needle-free, easy-to-use, and low-invasive vaccination method. The hydrogel patch-based TCI system induced immune responses against soluble antigens (Ags) like toxoids, but could not induce immune responses against particulate Ags. Here, as an effective TCI system against every form of Ag, we developed a dissolving microneedle array of three lengths (200, 300, or 800 mu m) made of hyaluronate as a novel TCI device. Unlike conventional microneedles, the microneedles of our dissolving microneedle arrays dissolved in the skin after insertion. Each dissolving microneedle array effectively delivered both soluble and particulate Ags under the stratum corneum. TCI using these dissolving microneedle arrays induced effective immune responses in rats regardless of the Ag form that were comparable to conventional vaccination using subcutaneous immunization. In addition, application of these dissolving microneedle arrays caused only slight skin irritation. These findings suggest that our TCI system can simply, safely, and effectively improve protective immune responses for every vaccine Ag. (C) 2012 Elsevier B.V. All rights reserved.
  • Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza, Kazuhiko Matsuo, Sachiko Hirobe, Yayoi Yokota, Yurika Ayabe, Masashi Seto, Ying-Shu Quan, Fumio Kamiyama, Takahiro Tougan, Toshihiro Horii, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF CONTROLLED RELEASE, JOURNAL OF CONTROLLED RELEASE, 160(3), 495 - 501, Jun. 2012 , Refereed
    Summary:Transcutaneous immunization (TCI) is an attractive alternative vaccination route compared to the commonly used injection systems. We previously developed a dissolving microneedle array for use as a TCI device, and reported that TCI with the dissolving microneedle array induced an immune response against model antigens. In the present study, we investigated the vaccination efficacy against tetanus and diphtheria, malaria, and influenza using this vaccination system. Our TCI system induced substantial increases in toxoid-specific IgG levels and toxin-neutralizing antibody titer and induced the production of anti-SE36 IgG, which could bind to malaria parasite. On influenza HA vaccination, robust antibody production was elicited in mice that provided complete protection against a subsequent influenza virus challenge. These findings demonstrate that TCI using a dissolving microneedle array can elicit large immune responses against infectious diseases. Based on these results, we are now preparing translational research for human clinical trials. (C) 2012 Elsevier B.V. All rights reserved.
  • Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria, Sachiko Hirobe, Kazuhiko Matsuo, Ying-Shu Quan, Fumio Kamiyama, Hironori Morito, Hideo Asada, Yusuke Takaya, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, VACCINE, VACCINE, 30(10), 1847 - 1854, Feb. 2012 , Refereed
    Summary:Transcutaneous immunization (TCI) is a non-invasive and easy-to-use vaccination method. We demonstrated the efficacy and safety of a transcutaneous vaccine formulation using a hydrogel patch in animal experiments. In the present study, we performed a clinical study to apply our TCI formulation for vaccination against tetanus and diphtheria in human. The TCI device was a hydrogel patch (antigen-free) applied to the left brachial medial skin of 22 healthy volunteers for 48 h. Next, the hydrogel patch, containing 2 mg tetanus toxoid (TT) and 2 mg diphtheria toxoid (DT) as the TCI formulation, was applied to 27 healthy volunteers for 24 h and some volunteers were vaccinated again by TCI formulation. For safety assessment, the patch application site was observed to assess local adverse events, and systemic adverse events were determined by a blood test. The antigen-free hydrogel patch and TCI formulation containing TT and DT did not induce local or systemic severe adverse events. For vaccine efficacy estimation, toxoid-specific serum antibody titers were determined by ELISA and the toxin-neutralizing activity of the induced antibody was evaluated in a passive-challenge experiment. The anti-TT IgG titer and the anti-DT IgG titer increased, and a significant effect was detected by paired t-test. The antibody titers were maintained at higher level than that before vaccination for at least 1 year. Moreover, toxoid-specific antibodies were produced by the second vaccination in some subjects. Antibodies induced by application of the TCI formulation neutralized the toxin and prevented toxic death in mice. In addition, changes in the skin condition due to application of the TCI formulation were observed under in vivo confocal Raman spectroscopy. The amount of water and patch components in the stratum corneum increased after application of the TCI formulation, suggesting that the change in the skin condition was related to antigen penetration. These data indicate that this easy-to-use TCI system induces an immune response without severe adverse reactions in humans. This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases. (C) 2012 Elsevier Ltd. All rights reserved.
  • Compositional Optimization and Safety Assessment of a Hydrogel Patch as a Transcutaneous Immunization Device, Kazuhiko Matsuo, Yumiko Ishii, Ying-Shu Quan, Fumio Kamiyama, Hideo Asada, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 34(12), 1835 - 1840, Dec. 2011 , Refereed
    Summary:The development of a simple, easy-to-use, and non-invasive vaccination system is in high demand. For transcutaneous immunization (TCI), we previously developed a hydrogel patch formulation that accelerates the penetration of an antigen (Ag) through the stratum corneum (SC) and effectively elicits Ag-specific immune responses. The present studies were performed to optimize the composition and assess the safety of the patch formulation. A hydrogel patch with a water content ratio of 5% more effectively induced an immune response compared to patches. with a different composition, suggesting that the moisture content of the hydrogel patch formulation has optimal ratio for SC hydration to promote Ag penetration through the SC. TCI using a hydrogel patch induced few local and systemic adverse reactions. Based on these results, we are now advancing translational research to evaluate the safety and efficacy of our novel TCI system in humans.
  • [Development of transcutaneous vaccine formulations for the infectious disease countermeasure]., Kazuhiko Matsuo, Naoki Okada, Shinsaku Nakagawa, Nihon rinsho. Japanese journal of clinical medicine, Nihon rinsho. Japanese journal of clinical medicine, 69(9), 1561 - 6, Sep. 2011 , Refereed
    Summary:The recent vigorous transnational migration of people and materials reflecting the development of transportation facilities have increased the global spread of infections. On the basis of this social background, the development of vaccination, which is the only fundamental prophylaxis, is in attention. Even if, however, rapid manufacture of vaccine antigen is actualized, there are several problems that vaccine is not easily spread across the developing country, because conventional vaccination is performed mainly by injection. Our group developed two transcutaneous vaccine devices which delivered antigens to antigen-presenting cells: a hydrogel patch and a dissolving microneedle patch. Our transcutaneous immunization system using these devices receives a high evaluation as novel, easy-to-use, and low-invasive vaccination method against infections from home and abroad.
  • Systemic distribution, nuclear entry and cytotoxicity of amorphous nanosilica following topical application, Hiromi Nabeshi, Tomoaki Yoshikawa, Keigo Matsuyama, Yasutaro Nakazato, Kazuhiko Matsuo, Akihiro Arimori, Masaaki Isobe, Saeko Tochigi, Sayuri Kondoh, Toshiro Hirai, Takanori Akase, Takuya Yamashita, Kohei Yamashita, Tokuyuki Yoshida, Kazuya Nagano, Yasuhiro Abe, Yasuo Yoshioka, Haruhiko Kamada, Takayoshi Imazawa, Norio Itoh, Shinsaku Nakagawa, Tadanori Mayumi, Shin-ichi Tsunoda, Yasuo Tsutsumi, BIOMATERIALS, BIOMATERIALS, 32(11), 2713 - 2724, Apr. 2011 , Refereed
    Summary:Currently, nanomaterials (NMs) with particle sizes below 100 nm have been successfully employed in various industrial applications in medicine, cosmetics and foods. On the other hand, NMs can also be problematic in terms of eliciting a toxicological effect by their small size. However, biological and/or cellular responses to NMs are often inconsistent and even contradictory. In addition, relationships among NMs physicochemical properties, absorbency, localization and biological responses are not yet well understood. In order to open new frontiers in medical, cosmetics and foods fields by the safer NMs, it is necessary to collect the information of the detailed properties of NMs and then, build the prediction system of NMs safety. The present study was designed to examine the skin penetration, cellular localization, and cytotoxic effects of the well-dispersed amorphous silica particles of diameters ranging from 70 nm to 1000 nm. Our results suggested that the well-dispersed amorphous nanosilica of particle size 70 nm (nSP70) penetrated the skin barrier and caused systemic exposure in mouse, and induced mutagenic activity in vitro. Our information indicated that further studies of relation between physicochemical properties and biological responses are needed for the development and the safer form of NMs. (C) 2011 Elsevier Ltd. All rights reserved.
  • Characterization of Transcutaneous Protein Delivery by a Hydrogel Patch in Animal, Human, and Tissue-Engineered Skin Models, Kazuhiko Matsuo, Yumiko Ishii, Ying-Shu Quan, Fumio Kamiyama, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 34(4), 586 - 589, Apr. 2011 , Refereed
    Summary:The development of a simple, easy-to-use, and noninvasive vaccination system is in high demand. For transcutaneous immunization (TCI), we previously reported that a hydrogel patch was an effective TCI device that accelerates antigen penetration through the stratum corneum in mouse and rat models. The present study was performed to characterize the transcutaneous protein delivery induced by the hydrogel patch in mouse, guinea pig, LWD pig, human, or tissue-engineered skin models, and to assess the activity of proteins delivered into the skin. The hydrogel patch promoted protein penetration through the stratum corneum in all skin models, indicating that our original hydrogel patch might have practical application for use in humans. In addition, proteins delivered into the skin by the hydrogel patch retained their activity, suggesting that the hydrogel patch is applicable for the delivery of therapies for other diseases as well. On the basis of these results, translational research in human is now in progress.
  • Transcutaneous vaccination using a hydrogel patch induces effective immune responses to tetanus and diphtheria toxoid in hairless rat, Kazuhiko Matsuo, Yumiko Ishii, Ying-Shu Quan, Fumio Kamiyama, Yohei Mukai, Yasuo Yoshioka, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF CONTROLLED RELEASE, JOURNAL OF CONTROLLED RELEASE, 149(1), 15 - 20, Jan. 2011 , Refereed
    Summary:Transcutaneous immunization (TCI) targeting the Langerhans cells (LCs) of the epidermal layer is a promising needle-free, easy-to-use, and non-invasive vaccination method. We developed a hydrogel patch formulation to promote the penetration of antigenic proteins into the stratum corneum. Here, we investigated the characteristics of the immune responses induced by this vaccination method and the vaccine efficacy of TCI using a hydrogel patch containing tetanus and diphtheria toxoids. Our TCI system induced toxoid-specific IgG production in an antigen dose-, patch area-, and application period-dependent manner. Moreover, IgG subclass analysis indicated that our TCI predominantly elicited a Th2-type immune response rather than a Th1-type immune response. Importantly, our TCI system induced antigen-specific immune memory based on the booster effect and showed potent efficacy, comparable to that of subcutaneous immunization in toxin-challenge experiments. On the basis of these results, we are now performing translational research to apply TCI for tetanus and diphtheria. (C) 2010 Elsevier B.V. All rights reserved.
  • A transcutaneous vaccination system using a hydrogel patch for viral and bacterial infection, Yumiko Ishii, Tomoko Nakae, Fumiko Sakamoto, Kazuhiko Matsuo, Keisuke Matsuo, Ying-Shu Quan, Fumio Kamiyama, Takuya Fujita, Akira Yamamoto, Shinsaku Nakagawa, Naoki Okada, JOURNAL OF CONTROLLED RELEASE, JOURNAL OF CONTROLLED RELEASE, 131(2), 113 - 120, Oct. 2008 , Refereed
    Summary:One of the most important anthropic missions is preventing the global spread of infectious diseases. Vaccination is the only available preventive treatment for infectious diseases, but the availability of vaccines in developing countries is not adequate. We report a simple, easy-to-use, noninvasive hydrogel patch transcutaneous vaccination system. Antigen (Ag)-specific IgG production was induced by applying an Ag-immersed patch to non-pretreated mouse auricle or hairless rat back skin. Immunofluorescence histochemical analysis revealed that Langerhans cells resident in the epidermal layer captured the antigenic proteins delivered by the hydrogel patch, which promoted the penetration of antigenic proteins through the stratum corneum, and that Ag-capturing Langerhans cells migrated into draining lymph nodes. Humoral immunity elicited by our transcutaneous vaccination system demonstrated neutralizing activity in both adenoviral infection and passive-challenge tetanus toxin experiments. The use of this hydrogel patch transcutaneous vaccination system will facilitate the global distribution of effective and convenient vaccines. (C) 2008 Elsevier B.V. All rights reserved.
  • Nanoparticles built by self-assembly of amphiphilic gamma-PGA can deliver antigens to antigen-presenting cells with high efficiency: A new tumor-vaccine carrier for eliciting effector T cells, Tomoaki Yoshikawa, Naoki Okada, Atsushi Oda, Keisuke Matsuo, Kazuhiko Matsuo, Hiroyuki Kayamuro, Yumiko Ishii, Tomoyo Yoshinaga, Takami Akagi, Mitsuru Akashi, Shinsaku Nakagawa, VACCINE, VACCINE, 26(10), 1303 - 1313, Mar. 2008 , Refereed
    Summary:Nanotechnology is a fundamental technology for designing and generating innovative carriers for biomacromolecular drugs. Biodegradable poly(- -glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers capable of delivering antigenic proteins to antigen -presenting cells (APCs) and eliciting potent immune responses based on antigen -specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathotogic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic (C) 2008 Elsevier Ltd. All rights reserved.
  • Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: Potential of the nanoparticulate cytosolic protein delivery carrier, Tomoaki Yoshikawa, Naoki Okada, Atsushi Oda, Kazuhiko Matsuo, Keisuke Matsuo, Yohei Mukai, Yasuo Yoshioka, Takami Akagi, Mitsuru Akashi, Shinsaku Nakagawa, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 366(2), 408 - 413, Feb. 2008 , Refereed
    Summary:Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines. (C) 2007 Published by Elsevier Inc.

Misc

  • Chemokine receptors and cell migration, 松尾一彦, 中山隆志, 日本血栓止血学会誌, 30, 4, 610‐618(J‐STAGE),   2019 , 10.2491/jjsth.30.610, https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201902244635586992
  • Search for chemokine receptor CCR3 selective antagonist as anti-allergic principles from mace, the arils of Myristica fragrans, Morikawa Toshio, Matsuo Kazuhiko, Hachiman Ikuko, Ninomiya Kiyofumi, Muraoka Osamu, Nakayama Takashi, Symposium on the Chemistry of Natural Products, symposium papers, 56, 0,   2018 07 19 , http://ci.nii.ac.jp/naid/130007399508
    Summary:<p>Chemokines play pivotal roles in health and disease by controlling migration and tissue localization of specific types of cells expressing their cognate receptors. They are grouped into four subfamilies (CXC, CC, CX3C, and XC) by the structural motif of the N-terminal conserved cysteine residues. Among the CC chemokine receptors, CCR3 is selectively expressed on eosinophils, basophils, and some Th2 cells, and plays an essential role in the pathogenesis of allergic diseases by modifying the kinetics of these cells. In the course of our characterization studies on anti-allergic principles from natural resources, we found that a methanol extract from mace, the arils of Myristica fragrans, showed inhibitory effect on eotaxin/CCL11-induced cell migration in L1.2 cells expressing CCR3 at a concentration of 100 mg/mL. Among the isolates from the extract, three new neolignans 3 (EC<sub>50</sub> = 1.62 mM), 4 (1.47 mM), and 5 (1.35 mM) were identified as the constituents responsible for the activity, and these activities were equivalent to that of SB328437 (EC<sub>50</sub> = 0.78 mM), a CCR3 selective antagonist. These results indicated that the neolignan constituents (3–5) are potential candeidates for the new anti-allergic agents.</p>
  • メース(Myristica fragrans,仮種皮)のケモカイン受容体CCR3アンタゴニスト様作用を指標とした抗アレルギー作用成分の探索, 森川敏生, 森川敏生, 八幡郁子, 松尾一彦, 西田枝里子, 二宮清文, 二宮清文, 義江修, 村岡修, 村岡修, 中山隆志, 食品薬学シンポジウム講演要旨集, 7th, 134‐136,   2017 10 10 , http://jglobal.jst.go.jp/public/201702219970879037
  • CCR4阻害剤はTregの筋肉組織への遊走を阻害することでワクチン効果を向上させる, 東山慎太郎, 松尾一彦, 松永奈緒子, 山田祐毅, 西脇敬二, 義江修, 中山隆志, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26PB‐am071S,   2017 , http://jglobal.jst.go.jp/public/201702227068290497
  • ケモカイン受容体CCR4の欠損はメラノーマ担癌モデルマウスの病態を増悪させる, 高橋周平, 松尾一彦, 小山篤, 西脇敬二, 義江修, 中山隆志, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26PB‐am068S,   2017 , http://jglobal.jst.go.jp/public/201702242388466738
  • CCR4欠損マウスおよびCCR6欠損マウスを用いたイミキモド誘発性乾癬の解析, 伊藤茉奈, 松尾一彦, 長沼孝典, 西脇敬二, 義江修, 中山隆志, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26PB‐am070S,   2017 , http://jglobal.jst.go.jp/public/201702254581423306
  • ケモカイン受容体CCR4の欠損はアトピー様皮膚炎の病態を改善させる, 木村勇太, 松尾一彦, 小森悠平, 畑中翔太, 西脇敬二, 義江修, 中山隆志, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26PB‐am069S,   2017 , http://jglobal.jst.go.jp/public/201702260154362718
  • ケモカイン受容体を標的とした天然由来シーズの探索研究(2):ロウバイカ(Chimonanthus praecox花蕾部)のCCR6およびCCR7アンタゴニスト活性成分, 森川敏生, 松尾一彦, 奥川修平, 奥川修平, 北川仁一朗, 北川仁一朗, 二宮清文, 中西勇介, 村岡修, 村岡修, 中山隆志, 中山隆志, 日本生薬学会年会講演要旨集, 63rd, 146,   2016 08 25 , http://jglobal.jst.go.jp/public/201602251743247114
  • 和漢薬ライブラリーを利用したケモカイン受容体CCR3及びCCR4のアンタゴニスト成分の探索, 北田 卓也, 松尾 一彦, 小泉 桂一, 義江 修, 中山 隆志, 日本薬学会年会要旨集, 135年会, 3, 167, 167,   2015 03
  • メースの機能性成分(4);ケモカイン受容体CCR3選択的アゴニスト作用成分の探索, 森川敏生, 八幡郁子, 松尾一彦, 二宮清文, 村岡修, 中山隆志, 日本生薬学会年会講演要旨集, 61st, 118,   2014 08 27 , http://jglobal.jst.go.jp/public/201402294364708616
  • 小児感染症の予防2014 I.ワクチンによる小児感染症の予防 12.次世代ワクチンの開発 2)「貼るワクチン」による感染症予防の試み, 松尾一彦, 岡田直貴, 中川晋作, 小児科臨床, 67, 4, 607, 614,   2014 04 05 , http://jglobal.jst.go.jp/public/201402280525481284
  • Search for chemokine receptor CCR3 selective antagonist as anti-allergic principles from mace, the arils of Myristica fragrans, Morikawa Toshio, Matsuo Kazuhiko, Hachiman Ikuko, Ninomiya Kiyofumi, Muraoka Osamu, Nakayama Takashi, Symposium on the Chemistry of Natural Products, symposium papers, 56, 0,   2014 , http://ci.nii.ac.jp/naid/130007399508
    Summary:<p>Chemokines play pivotal roles in health and disease by controlling migration and tissue localization of specific types of cells expressing their cognate receptors. They are grouped into four subfamilies (CXC, CC, CX3C, and XC) by the structural motif of the N-terminal conserved cysteine residues. Among the CC chemokine receptors, CCR3 is selectively expressed on eosinophils, basophils, and some Th2 cells, and plays an essential role in the pathogenesis of allergic diseases by modifying the kinetics of these cells. In the course of our characterization studies on anti-allergic principles from natural resources, we found that a methanol extract from mace, the arils of Myristica fragrans, showed inhibitory effect on eotaxin/CCL11-induced cell migration in L1.2 cells expressing CCR3 at a concentration of 100 mg/mL. Among the isolates from the extract, three new neolignans 3 (EC<sub>50</sub> = 1.62 mM), 4 (1.47 mM), and 5 (1.35 mM) were identified as the constituents responsible for the activity, and these activities were equivalent to that of SB328437 (EC<sub>50</sub> = 0.78 mM), a CCR3 selective antagonist. These results indicated that the neolignan constituents (3–5) are potential candeidates for the new anti-allergic agents.</p>
  • 臨床研究におけるインフルエンザ経皮ワクチン製剤の免疫誘導特性に関する解析, 廣部祥子, 小豆澤宏明, 花房崇明, 松尾一彦, 権英淑, 神山文男, 片山一朗, 岡田直貴, 中川晋作, 日本薬剤学会年会講演要旨集(Web), 28th, 23-3-14 (WEB ONLY), 208,   2013 04 26 , http://jglobal.jst.go.jp/public/201302242210411974
  • 和漢薬の科学基盤 共同研究による先駆的統合的解明 標準和漢薬ライブラリーを用いたケモカイン受容体CCR3およびCCR4アンタゴニストの探索 アレルギー疾患を標的として, 中山 隆志, 田中 宏幸, 松尾 一彦, 小泉 桂一, 義江 修, 日本薬学会年会要旨集, 133年会, 1, 146, 146,   2013 03
  • Application of Poly(γ-Glutamic Acid)-Based Nanoparticles as Antigen Delivery Carriers in Cancer Immunotherapy, Kazuhiko Matsuo, Naoki Okada, Shinsaku Nakagawa, Bio-Nanotechnology: A Revolution in Food, Biomedical and Health Sciences, 487, 505,   2013 01 04 , 10.1002/9781118451915.ch28, https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84887162799&origin=inward
    Summary:Establishing a technique that will efficiently deliver tumor-associated antigens to antigen-presenting cells is expected to improve the efficacy of tumor vaccine therapies. We have succeeded in augmenting tumor immunity based on the efficient induction of cytotoxic T cells specific to tumor-associated antigens using poly(γ-glutamic acid)-based nanoparticles as antigen carriers. In this review, we outline the utility of nanoparticle drug delivery technology in tumor vaccine therapy, based mainly on our data obtained using poly(γ-glutamic acid)-based nanoparticles. © 2013 John Wiley & Sons, Ltd.
  • Development of Transcutaneous Vaccination System for Infectious Disease Countermeasure, Kazuhiko Matsuo, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 132, 12, 1443, 1450,   2012 12 , 10.1248/yakushi.12-00205, http://ci.nii.ac.jp/naid/130002489522
    Summary:The recent vigorous transnational migration of people and materials reflecting the development of transportation facilities, changes in social structure, and war disasters has increased the global spread of emerging and re-emerging infections. Once, as the 2009 pandemic influenza A (H1N1) virus, person-to-person transmission was achieved, the spread of pandemic cannot be contained in reality. Thus enhancement of the crisis-management structure against pandemic is critically important to maintain national function. On the basis of this social background, the development of vaccination, which is the only fundamental prophylaxis, is in attention, and earliest possible establishment of system that supply mass-vaccines in a short time is required. Even if, however, rapid manufacture of vaccine antigen is actualized, there are several problems that vaccine is not easily spread across the developing country and mass vaccination is not performed immediately at the time of the crisis, because conventional vaccination is performed mainly by injection. Our research group developed transcutaneous vaccine devices; a hydrogel patch and a dissolving microneedle array which delivered antigens to antigen-presenting cells in the epidermal layer. Our transcutaneous vaccination system receives a high evaluation as novel, easy-to-use, and less-invasive vaccination method against infections from home and abroad. In this review, we introduce the research progress resulted from our basic, preclinical, and clinical study for practical use.
  • インフルエンザHA抗原装填マイクロニードルパッチ製剤のヒトにおける安全性・有効性の検証, 廣部祥子, 小豆澤宏明, 花房崇明, 仁木一順, 松尾一彦, 権英淑, 神山文男, 片山一朗, 向洋平, 岡田直貴, 中川晋作, 日本DDS学会学術集会プログラム予稿集, 28th, 128, 128,   2012 06 05 , http://jglobal.jst.go.jp/public/201202223777767689
  • 皮膚内溶解型マイクロニードルを用いた経皮ワクチン製剤の物理化学的特性, 中川岳志, 平石恭大, 権英淑, 神山文男, 松尾一彦, 向洋平, 岡田直貴, 中川晋作, 日本薬剤学会年会講演要旨集(Web), 27th, 26-4-19 (WEB ONLY),   2012 04 25 , http://jglobal.jst.go.jp/public/201302217319179376
  • 新型インフルエンザパンデミックに即時対応できる経皮ワクチンシステムの開発, 仁木一順, 松尾一彦, 廣部祥子, 権英淑, 神山文男, 向洋平, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 132nd, 4, 207, 207,   2012 03 05 , http://jglobal.jst.go.jp/public/201202211009762904
  • 皮膚内溶解型マイクロニードルを用いたインフルエンザ経皮ワクチンの臨床研究, 廣部祥子, 小豆澤宏明, 花房崇明, 松尾一彦, 権英淑, 神山文男, 片山一朗, 向洋平, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 16th, 115,   2012 , http://jglobal.jst.go.jp/public/201202255799208909
  • 皮膚内溶解型マイクロニードルを用いたインフルエンザ経皮ワクチンの開発, 松尾一彦, 横田やよい, 廣部祥子, 権英淑, 神山文男, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 15th, 108,   2011 11 21 , http://jglobal.jst.go.jp/public/201102214653529643
  • 経皮ワクチンデバイス―皮膚内溶解型マイクロニードル―のヒトにおける安全性試験, 西内翠, 廣部祥子, 松尾一彦, 権英淑, 神山文男, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 15th, 106,   2011 11 21 , http://jglobal.jst.go.jp/public/201102276726353161
  • 経皮ワクチン(貼るワクチン)におけるToll様受容体リガンドのアジュバント効果, ZHAI You, 松尾一彦, 齋塲雄貴, 権英淑, 神山文男, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 15th, 107,   2011 11 21 , http://jglobal.jst.go.jp/public/201102287083365819
  • アルツハイマー病モデルマウスにおけるアミロイドβ装填マイクロニードル製剤の経皮ワクチン効果, 岡本英揚, 松尾一彦, 岡田直貴, 中川晋作, 日本免疫学会総会・学術集会記録, 40, 127,   2011 11 07 , http://jglobal.jst.go.jp/public/201102207813454690
  • 経皮ワクチン製剤のヒトにおける安全性および有効性の評価, 廣部祥子, 松尾一彦, 岡田直貴, 中川晋作, 日本免疫学会総会・学術集会記録, 40, 127,   2011 11 07 , http://jglobal.jst.go.jp/public/201102258680925752
  • 皮膚内溶解型マイクロニードルを応用した経皮免疫製剤の感染防御効果, 松尾一彦, 廣部祥子, 岡田直貴, 中川晋作, 日本免疫学会総会・学術集会記録, 40, 127,   2011 11 07 , http://jglobal.jst.go.jp/public/201102289551621340
  • The development of microneedle-based transcutaneous immunization system, 松尾 一彦, 岡田 直貴, 中川 晋作, 綜合臨床, 60, 11, 2211, 2214,   2011 11 , http://ci.nii.ac.jp/naid/40019055325
  • 皮膚内溶解型マイクロニードルを用いたアトピー性皮膚炎治療法の可能性, 仁木一順, 廣部祥子, 松尾一彦, 権英淑, 神山文男, 向洋平, 岡田直貴, 中川晋作, Aesthetic Dermatol, 21, 2, 180, 180,   2011 09 10 , http://jglobal.jst.go.jp/public/201102210813576540
  • 皮膚内溶解型マイクロニードルを用いた貼るワクチンの実用化に向けて, 廣部祥子, 松尾一彦, 横田やよい, 権英淑, 神山文男, 小豆澤宏明, 片山一朗, 森川彰子, 井上龍巳, 角田秀信, 向洋平, 岡田直貴, 中川晋作, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 10th, 32,   2011 09 , http://jglobal.jst.go.jp/public/201102255391617536
  • 皮膚内溶解型マイクロニードルを用いたアルツハイマー型認知症に対する経皮ワクチン療法の開発, 岡本英揚, 松尾一彦, 権英淑, 神山文男, 向洋平, 岡田直貴, 中川晋作, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 10th, 33,   2011 09 , http://jglobal.jst.go.jp/public/201102296469600358
  • ワクチン II.ワクチン基礎研究の最新動向と展望 感染症予防対策に資する経皮免疫製剤(貼るワクチン)の開発, 松尾一彦, 岡田直貴, 中川晋作, 日本臨床, 69, 9, 1561, 1566,   2011 09 01 , http://jglobal.jst.go.jp/public/201102280713672567
  • 皮膚内溶解型マイクロニードルの穿刺特性および安全性に関する臨床研究, 廣部祥子, 松尾一彦, 権英淑, 神山文男, 小豆澤宏明, 片山一朗, 鈴木博, 向洋平, 岡田直貴, 中川晋作, Drug Delivery System, 26, 3, 312, 312,   2011 05 28 , http://jglobal.jst.go.jp/public/201102212223856109
  • 生分解性マイクロニードルの安全性評価に関する臨床研究, 廣部祥子, 松尾一彦, 平石恭大, ZHAI You, 権英淑, 神山文男, 小豆澤宏明, 片山一朗, 鈴木博, 向洋平, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 131st, 4, 188, 188,   2011 03 05 , http://jglobal.jst.go.jp/public/201102245306550198
  • 生分解性マイクロニードルを応用したアトピー性皮膚炎治療法の可能性, 仁木一順, 松尾一彦, 廣部祥子, 権英淑, 神山文男, 向洋平, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 131st, 4, 189, 189,   2011 03 05 , http://jglobal.jst.go.jp/public/201102234031751986
  • 臨床研究用生分解性マイクロニードルの作製と機能評価, ZHAI You, 松尾一彦, 権英淑, 神山文男, 向洋平, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 131st, 4, 189, 189,   2011 03 05 , http://jglobal.jst.go.jp/public/201102234794668109
  • 生分解性マイクロニードルを用いたインフルエンザ経皮ワクチンの有効性, 松尾一彦, 横田やよい, 権英淑, 神山文男, 鎌田良男, 向洋平, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 131st, 4, 189, 189,   2011 03 05 , http://jglobal.jst.go.jp/public/201102252178634142
  • 生分解性マイクロニードルの経皮ワクチンデバイスとしての特性, 松尾一彦, 横田やよい, てき優, 権英淑, 神山文男, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 14th, 71,   2010 11 10 , http://jglobal.jst.go.jp/public/201002253260492908
  • 経皮免疫製剤「貼るワクチン」のヒトにおける安全性および有効性の検証, 廣部祥子, 松尾一彦, 権英淑, 神山文男, 浅田秀夫, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 14th, 70,   2010 11 10 , http://jglobal.jst.go.jp/public/201002262374096319
  • 生分解性マイクロニードルを応用した経皮ワクチン製剤の有効性評価, 岡田直貴, 松尾一彦, 横田やよい, 廣部祥子, 権英淑, 神山文男, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 14th, 72,   2010 11 10 , http://jglobal.jst.go.jp/public/201002280583419794
  • 生分解性マイクロニードルを用いたマラリア経皮ワクチン製剤の開発, 松尾一彦, 綾部有里香, てき優, 権英淑, 神山文男, 堀井俊宏, 向洋平, 岡田直貴, 中川晋作, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 9th, 35,   2010 09 , http://jglobal.jst.go.jp/public/201002227723499205
  • 親水性ゲルパッチによる抗原の角質層透過促進機構に関する検討, 岡本英揚, 松尾一彦, 川合泰明, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Delivery System, 25, 3, 311, 311,   2010 05 28 , http://jglobal.jst.go.jp/public/201002262771325510
  • 破傷風・ジフテリア経皮ワクチン製剤のヒトにおける安全性・有効性の検証, 廣部祥子, 松尾一彦, 権英淑, 神山文男, 浅田秀夫, 高矢雄介, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Delivery System, 25, 3, 311, 311,   2010 05 28 , http://jglobal.jst.go.jp/public/201002230097132923
  • 生分解性マイクロニードルの経皮ワクチンデバイスとしての特性, 横田やよい, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Delivery System, 25, 3, 311, 311,   2010 05 28 , http://jglobal.jst.go.jp/public/201002251348382565
  • 多種多様な抗原に適用できる新規経皮ワクチン製剤の開発, 齋塲雄貴, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Delivery System, 25, 3, 312, 312,   2010 05 28 , http://jglobal.jst.go.jp/public/201002297685708197
  • アルツハイマー病に対する治療効果を狙った経皮ワクチン療法の開発, 亀井数正, 松尾一彦, 川合泰明, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Delivery System, 25, 3, 312, 312,   2010 05 28 , http://jglobal.jst.go.jp/public/201002203311089057
  • マラリア撲滅に向けた新規経皮ワクチン製剤の開発, 松尾一彦, 綾部有里香, 権英叔, 神山文男, 堀井俊宏, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Delivery System, 25, 3, 312, 312,   2010 05 28 , http://jglobal.jst.go.jp/public/201002295926919434
  • ワクチンに関する最新の話題―新しいワクチン時代の幕開け 新しいワクチン開発 感染症予防対策に向けた新規経皮ワクチン製剤の開発, 松尾一彦, 岡田直貴, 中川晋作, 臨床と微生物, 37, 3, 207, 212,   2010 05 25 , http://jglobal.jst.go.jp/public/201002291296047713
  • ワクチンの新たな展開 6 新規経皮ワクチンデバイスを用いた「貼るワクチン」の開発, 松尾一彦, QUAN Ying‐Shu, 岡田直貴, 中川晋作, Bio Clinica, 25, 5, 401, 405,   2010 05 10 , http://jglobal.jst.go.jp/public/201002285718955707
  • 感染症パンデミックの抑止に貢献する新規経皮ワクチン製剤の開発, 松尾一彦, 岡田直貴, 中川晋作, 薬剤学, 70, Supplement, 68, 68,   2010 04 20 , http://jglobal.jst.go.jp/public/201002259452916963
  • 感染症対策に資する画期的「貼るワクチン」の開発, 松尾一彦, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 1, 382,   2010 03 05 , http://jglobal.jst.go.jp/public/201002209073817071
  • 「貼るワクチン」の開発 VII~生分解性マイクロニードルを用いたインフルエンザワクチンの開発~, 川端洋輝, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 163,   2010 03 05 , http://jglobal.jst.go.jp/public/201002216400433149
  • 「貼るワクチン」の開発 III~生分解性マイクロニードルによる経皮抗原デリバリーに関する検討~, 横田やよい, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 163,   2010 03 05 , http://jglobal.jst.go.jp/public/201002230474955549
  • 「貼るワクチン」の開発 V~生分解性マイクロニードルを用いた破傷風・ジフテリアワクチンの開発~, 廣部祥子, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 163,   2010 03 05 , http://jglobal.jst.go.jp/public/201002237599300450
  • 「貼るワクチン」の開発 I~親水性ゲルパッチによる抗原蛋白質の角質層透過に関する検討~, 岡本英揚, 川合泰明, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 162,   2010 03 05 , http://jglobal.jst.go.jp/public/201002238705338026
  • 「貼るワクチン」の開発 IV~生分解性マイクロニードルによる可溶性抗原および粒子状抗原に対する免疫誘導~, 瀬戸正志, 松尾一彦, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 163,   2010 03 05 , http://jglobal.jst.go.jp/public/201002263164603893
  • 「貼るワクチン」の開発 II~親水性ゲルパッチを用いた経皮ワクチンの臨床研究~, 齊塲雄貴, 松尾一彦, 権英淑, 神山文男, 浅田秀夫, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 163,   2010 03 05 , http://jglobal.jst.go.jp/public/201002275196515110
  • 「貼るワクチン」の開発 VI~生分解性マイクロニードルを用いたマラリアワクチンの開発~, 綾部有里香, 松尾一彦, 権英淑, 神山文男, 堀井俊宏, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 130th, 4, 163,   2010 03 05 , http://jglobal.jst.go.jp/public/201002299628571323
  • Development of transcutaneous vaccine formulations based on DDS technology, Kazuhiko Matsuo, Naoki Okada, Shinsaku Nakagawa, Drug Delivery System, 25, 1, 8, 14,   2010 , 10.2745/dds.25.8, http://ci.nii.ac.jp/naid/10026238206
    Summary:Transcutaneous immunization (TCI) system utilizing skin immune function is a promising needle-free, easy-to-use, and non-invasive vaccination method instead of conventional injectable vaccination method. For effective TCI system, it is essential to establish the fundamental techniques that antigenic proteins were delivered to antigen-presenting cells in the epidermal layer. In this review, we give outline of recent research trend about antigenic protein delivery techniques for TCI and introduce our basic and preclinical research about TCI using our original hydrogel patch formulation containing antigenic proteins.
  • 生分解性マイクロニードルを応用した経皮ワクチンの開発, 松尾一彦, 横田やよい, 廣部祥子, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 8th, 58,   2009 11 02 , http://jglobal.jst.go.jp/public/201002288064540595
  • 新規香粧品素材として注目されるナノシリカの経皮リスクに関する基礎検討, 松尾一彦, 免山智行, 角田慎一, 堤康央, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本香粧品学会誌, 33, 3, 218, 219,   2009 09 30 , http://jglobal.jst.go.jp/public/200902299851083941
  • 親水性ゲルパッチを用いた経皮免疫製剤の免疫誘導特性ならびに安全性, 松尾一彦, 石井裕美子, 川合泰明, 齋塲雄貴, 瀬戸正志, 横田やよい, 権英淑, 神山文男, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 13th, 137,   2009 08 10 , http://jglobal.jst.go.jp/public/200902238613263894
  • 親水性ゲルパッチを用いた経皮ワクチンにおけるToll様受容体リガンドのアジュバント効果, 齋塲雄貴, 松尾一彦, 石井裕美子, 川合泰明, 瀬戸正志, 横田やよい, 権英淑, 神山文男, 岡田直貴, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 13th, 138,   2009 08 10 , http://jglobal.jst.go.jp/public/200902255999038743
  • 親水性ゲルパッチを用いた経皮免疫製剤のアジュバント併用時の有効性評価, 齋場雄貴, 松尾一彦, 石井裕美子, 川合泰明, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, Drug Deliv Syst, 24, 3, 322, 322,   2009 06 09 , http://jglobal.jst.go.jp/public/200902222224909904
  • ナノシリカの皮膚透過性と経皮リスクに関する基礎検討, 松尾一彦, 免山智行, 角田慎一, 堤康央, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 129th, 4, 286, 286,   2009 03 05 , http://jglobal.jst.go.jp/public/200902209159575401
  • 破傷風・ジフテリアに対する経皮免疫製剤の実用化に向けた基礎的検討, 川合泰明, 松尾一彦, 石井裕美子, 齋塲雄貴, 権英淑, 神山文男, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 129th, 4, 165, 165,   2009 03 05 , http://jglobal.jst.go.jp/public/200902240002182400
  • ジフテリアトキソイドおよび破傷風トキソイドを用いた「貼るワクチン」の開発, 中川晋作, 石井裕美子, 松尾一彦, 権英淑, 神山文男, 岡田直貴, 日本ワクチン学会学術集会プログラム・抄録集, 12th, 99,   2008 10 10 , http://jglobal.jst.go.jp/public/200902233813627570
  • 親水性ゲルパッチを用いた「貼るワクチン」の開発と経皮免疫造成機構の解明, 石井裕美子, 岡田直貴, 松尾圭祐, 松尾一彦, 権英淑, 神山文男, 藤田卓也, 中川晋作, 日本ワクチン学会学術集会プログラム・抄録集, 11th, 108,   2007 11 11 , http://jglobal.jst.go.jp/public/200902285968175943
  • 抗原送達キャリアーとしてγ-PGAナノ粒子を用いた経鼻投与型癌ワクチンの開発(Development of nasal administration-type cancer vaccine using γ-PGA nanoparticle as an antigen delivery carrier), 松尾 一彦, 松尾 圭祐, 赤木 隆美, 明石 満, 向 洋平, 吉岡 靖雄, 岡田 直貴, 中川 晋作, 日本癌学会総会記事, 66回, 425, 425,   2007 08
  • 抗原内包γ‐PGAナノ粒子を用いた経鼻投与型癌ワクチンの開発, 松尾一彦, 小泉勇人, 松尾圭祐, 赤木隆美, 明石満, 藤田卓也, 山本昌, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 薬剤学, 67, Supplement, 373, 373,   2007 05 10 , http://jglobal.jst.go.jp/public/200902227917879261
  • 抗原内包γ‐PGAナノ粒子の経鼻投与による腫瘍免疫誘導, 小泉勇人, 松尾一彦, 坂本史子, 溝内亜希子, 松尾圭祐, 吉川友章, 赤木隆美, 明石満, 中川晋作, 藤田卓也, 山本昌, 岡田直貴, 日本薬学会年会要旨集, 127th, 3, 86, 86,   2007 03 05 , http://jglobal.jst.go.jp/public/200902201713300443
  • 抗原内包γ‐PGAナノ粒子の免疫誘導機構と安全性に関する検討, 松尾圭祐, 吉川友章, 萱室裕之, 松尾一彦, 赤木隆美, 明石満, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 127th, 3, 86, 86,   2007 03 05 , http://jglobal.jst.go.jp/public/200902212776321175
  • γ‐PGAナノ粒子の抗原送達キャリアー特性とその癌免疫療法への応用, 松尾圭祐, 吉川友章, 松尾一彦, 石井裕美子, 吉永知世, 赤木隆美, 明石満, 向洋平, 吉岡靖雄, 岡田直貴, 中川晋作, 遺伝子・デリバリー研究会シンポジウム要旨集, 7th, 54,   2007 , http://jglobal.jst.go.jp/public/200902246244625321
  • 抗原内包γ‐PGAナノ粒子を用いた癌免疫療法におけるエフェクター細胞機能および安全性の評価, 萱室裕之, 松尾圭祐, 松尾一彦, 吉川友章, 明石満, 岡田直貴, 中川晋作, 日本免疫学会総会・学術集会記録, 36, 37,   2006 11 15 , http://jglobal.jst.go.jp/public/200902234650264773
  • 癌免疫療法における抗原送達キャリアーとしてのγ‐PGAナノ粒子の有用性, 松尾一彦, 吉川友章, 赤木隆美, 明石満, 岡田直貴, 中川晋作, 日本癌学会学術総会記事, 65th, 321,   2006 08 28 , http://jglobal.jst.go.jp/public/200902205860842117
  • 抗原提示細胞への抗原蛋白質デリバリーにおけるγ‐PGAナノ粒子の有用性, 小田淳史, 吉川友章, 丹羽貴子, 松尾一彦, 萱室裕之, 堤康央, 赤木隆美, 明石満, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 126th, 2, 128, 128,   2006 03 06 , http://jglobal.jst.go.jp/public/200902254664367207
  • 抗原蛋白質を内包したγ‐PGAナノ粒子の特性評価と抗腫ようワクチンキャリアーへの応用, 吉川友章, 小田淳史, 丹羽貴子, 松尾一彦, 萱室裕之, 堤康央, 赤木隆美, 明石満, 岡田直貴, 中川晋作, 日本薬学会年会要旨集, 126th, 2, 128,   2006 03 06 , http://jglobal.jst.go.jp/public/200902294591045569
  • 腫ようワクチンキャリアーとしての両親媒化ポリγ‐グルタミン酸ナノ粒子の機能評価, 萱室裕之, 吉川友章, 小田淳史, 松尾一彦, 赤木隆美, 明石満, 岡田直貴, 中川晋作, 薬剤学, 66, Supplement, 196,   2006 02 24 , http://jglobal.jst.go.jp/public/200902272772009625
  • 両親媒化ポリグルタミン酸を用いた新規生分解性ワクチンキャリアの開発と抗腫ようワクチンへの応用―3, 飯田恵介, 吉川友章, 小田淳史, 丹羽貴子, 松尾一彦, 萱室裕之, 堤康央, 赤木隆美, 明石満, 中川晋作, 日本免疫学会総会・学術集会記録, 35, 129,   2005 11 15 , http://jglobal.jst.go.jp/public/200902250205147266
  • 両親媒化ポリγ‐グルタミン酸を用いた新規生分解性ナノキャリアの開発と抗腫ようワクチンへの応用―2, 小田淳史, 吉川友章, 丹羽貴子, 飯田恵介, 松尾一彦, 萱室裕之, 堤康央, 赤木隆美, 明石満, 中川晋作, 日本免疫学会総会・学術集会記録, 35, 128,   2005 11 15 , http://jglobal.jst.go.jp/public/200902257101207920
  • 変異型抗アポトーシス蛋白質Bcl‐xFNK発現樹状細胞を用いた抗腫よう効果に関する検討, 丹羽貴子, 吉川友章, 小田淳史, 飯田恵介, 松尾一彦, 萱屋裕之, 岡田直貴, 堤康央, 水口裕之, 中川晋作, 日本免疫学会総会・学術集会記録, 35, 120,   2005 11 15 , http://jglobal.jst.go.jp/public/200902267060626349
  • 両親媒化ポリグルタミン酸を用いた新規生分解性ワクチンキャリアの開発と抗腫ようワクチンへの応用―1, 吉川友章, 小田淳史, 丹羽貴子, 飯田恵介, 松尾一彦, 萱室裕之, 堤康央, 赤木隆美, 明石満, 中川晋作, 日本免疫学会総会・学術集会記録, 35, 128,   2005 11 15 , http://jglobal.jst.go.jp/public/200902279660621756
  • ワクチンキャリアとしてのポリアミノ酸由来生分解性ナノ粒子の有用性評価―2, 小田淳史, 吉川友章, 丹羽貴子, 飯田恵介, 松尾一彦, 下川摩里子, 堤康央, 赤木隆美, 明石満, 中川晋作, Drug Delivery System, 20, 3, 363,   2005 07 06 , http://jglobal.jst.go.jp/public/200902202050201680
  • 活性増強変異型抗アポトーシス蛋白質Bcl‐xFNK発現樹状細胞を用いた腫ようワクチン療法, 丹羽貴子, 吉川友章, 小田淳史, 飯田恵介, 松尾一彦, 下川摩里子, 岡田直貴, 堤康央, 水口裕之, 中川晋作, Drug Delivery System, 20, 3, 363,   2005 07 06 , http://jglobal.jst.go.jp/public/200902270553500710
  • ワクチンキャリアとしてのポリアミノ酸由来生分解性ナノ粒子の有用性評価―1, 吉川友章, 小田淳史, 丹羽貴子, 飯田恵介, 松尾一彦, 下川摩里子, 堤康央, 赤木隆美, 明石満, 中川晋作, Drug Delivery System, 20, 3, 362,   2005 07 06 , http://jglobal.jst.go.jp/public/200902297948080537
  • Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza (vol 160, pg 495, 2012), Kazuhiko Matsuo, Sachiko Hirobe, Yayoi Yokota, Yurika Ayabe, Masashi Seto, Ying-Shu Quan, Fumio Kamiyama, Takahiro Tougan, Toshihiro Horii, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF CONTROLLED RELEASE, 184, 18, 19,   2014 06 , 10.1016/j.jconrel.2014.04.001
  • A low-invasive and effective transcutaneous immunization system using a novel dissolving microneedle array for soluble and particulate antigens (vol 161, pg 10, 2012), Kazuhiko Matsuo, Yayoi Yokota, You Zhai, Ying-Shu Quan, Fumio Kamiyama, Yohei Mukai, Naoki Okada, Shinsaku Nakagawa, JOURNAL OF CONTROLLED RELEASE, 184, 9, 9,   2014 06 , 10.1016/j.jconrel.2014.04.002
  • Development of vaccine adjuvant targeting the chemokine-chemokine receptor axis, Kazuhiko Matsuo, Drug Delivery System, 29, 3, 246, 247,   2014 , 10.2745/dds.29.246