Development of novel depot-forming bioabsorbable recombinant elastomers for immunoresponse augmentation

• Project/Area Number: 26460050
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Asai Daisuke 聖マリアンナ医科大学, 医学部, 助教 (10423485)
• Co-Investigator(Kenkyū-buntansha): 福田 靖 国立感染症研究所, 細菌第二部, 主任研究官 (80270651)
• Co-Investigator(Renkei-kenkyūsha): KATAYAMA Yoshiki 九州大学, 工学部, 教授 (70284528)
• Research Collaborator: MOROKUMA Kazunori ; SHIBAYAMA Keigo
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 薬物デポ / 生体材料 / DDS / 注射ゲル / 徐放 / エラスチン / ワクチン抗原 / ワクチン / アジュバント

Outline of Final Research Achievements

The frequency of administration of antigen must be done for enhanced immunoresponses to repeated exposures to the same antigens. In the context of vaccine compliance, versatile prolonged-release antigen delivery platforms with single injection are needed. We approached this issue by in situ formation of antigen-containing implants using recombinant protein polymer hydrogels, and demonstrate its utility as an injectable antigen depot capable of sustained release of tetanus toxoid. The novelty of this work stems from the genetically encoded design of these peptide polymers, which enables key molecular parameters that control the properties of the hydrogel to be precisely specified at the genetic level for antigens. Our hydrogel system may hold the promise of tailor-made long-lasting depot systems for a variety of antigens, aiming to design single-injection-type of vaccines.

Research Products

• [Journal Article] Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2) (2016)
  • Author(s): Asai, D., Murata, M., Toita, R., Kawano, T., Nakashima, H., and Kang, J.H.
  • Journal Title: Amino Acids Volume: 48 Issue: 12 Pages: 2875-2880
  • DOI: 10.1007/s00726-016-2345-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reversal of efflux of an anticancer drug in human drug-resistant breast cancer cells by inhibition of protein kinase Cα (PKCα) activity (2016)
  • Author(s): Kim, C.W., Asai, D., Kang, J.H., Kishimura, A., Mori, T., and Katayama, Y.
  • Journal Title: Tumor Biol. Volume: 37 Issue: 2 Pages: 1901-1908
  • DOI: 10.1007/s13277-015-3963-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Spatiotemporally photoradiation-controlled intratumoral depot for combination of brachytherapy and photodynamic therapy for solid tumor (2016)
  • Author(s): Mukerji, R., Schaal, J., Li, X., Bhattacharyya, J., Asai, D., Zalutsky, M.R, Chilkoti, A., and Liu, W.
  • Journal Title: Biomaterials Volume: 79 Pages: 79-87
  • DOI: 10.1016/j.biomaterials.2015.11.064
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor (2015)
  • Author(s): Takenaga, M., Yamamoto, Y., Takeuchi T., Ohta, Y., Tokura, Y., Hamaguchi, A., Asai, D., Nakashima, H., Oishi, S., and Fujii, N.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 463 Issue: 3 Pages: 222-228
  • DOI: 10.1016/j.bbrc.2015.05.029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Monitoring of phosphorylated peptides by radioactive assay and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (2015)
  • Author(s): Kang, J.H., Asai, D., Toita, R., Kawano, T., and Murata, M.
  • Journal Title: Amino Acids Volume: 47 Issue: 11 Pages: 2377-2383
  • DOI: 10.1007/s00726-015-2025-y
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Antibody internalization into living cell via crosslinker-mediated endocytosis (2015)
  • Author(s): Funamoto D, Asai D, Sato K, Yamaguchi Y, Kim CW, Sato H, Nakhaei E, Matsumoto S, Yoshikawa T, Sasaki K, Yamamoto T, Kishimura A, Mori T, and Katayama Y
  • Journal Title: Chem. Lett. Volume: 44 Issue: 4 Pages: 468-470
  • DOI: 10.1246/cl.141157
  • NAID: 130005062125
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tandemly repeated peptide for cancer-specific gene carrier prepared by native chemical ligation (2015)
  • Author(s): Funamoto D, Asai D, Kim CW, Nakamura Y, Lee EK, Nobori T, Niidome T, Mori T, and Katayama Y
  • Journal Title: Chem. Lett. Volume: 44 Issue: 4 Pages: 474-476
  • DOI: 10.1246/cl.141121
  • NAID: 130005062141
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression and characterization of myristoylatedpreS1-conjugated nanocages for targeted cell delivery (2014)
  • Author(s): Murata M, Piao JS, Narahara S, Kawano T, Hamano N, Kang JH, Asai D, Ugawa R, Hashizume M,
  • Journal Title: Protein Expressionand Purification Volume: 110 Pages: 52-56
  • DOI: 10.1016/j.pep.2014.12.001
  • Peer Reviewed / Open Access
• [Presentation] 人工エラスチンポリペプチド：破傷風トキソイドデポ製剤への最適化 (2016)
  • Author(s): 浅井大輔、福田靖、諸熊一則、山口優子、Ashutosh Chilkoti、柴山恵吾、中島秀喜
  • Organizer: 第３２回日本ＤＤＳ学会学術集会
  • Place of Presentation: グランシップ（静岡県静岡市）
  • Year and Date: 2016-06-30
• [Presentation] 新規合成KSP阻害剤のヒト卵巣がんに対する抗腫瘍効果 (2016)
  • Author(s): 武永美津子、竹内智起、山本有貴、都倉享恵、新美純、濱口明美、太田有紀、浅井大輔、大石真也、中島秀喜、藤井信孝
  • Organizer: 日本薬学会第１３６年会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
  • Year and Date: 2016-03-26
• [Presentation] マクロファージを選択的に認識する機能性ナノ分子の創製 (2015)
  • Author(s): 姜貞勲、戸井田力、浅井大輔、村田正治
  • Organizer: 第８８回日本生化学大会/第３８回日本分子生物学会 合同大会（BMB2015）
  • Place of Presentation: 神戸ポートアイランド（神戸市中央区）
  • Year and Date: 2015-12-01
• [Presentation] 破傷風トキソイドを用いた人工エラスチン蛋白のアジュバントとしての可能性 (2015)
  • Author(s): 福田靖、浅井大輔、山口優子、諸熊一則、Ashutosh Chilkoti、中島秀喜、柴山恵吾
  • Organizer: 第１９回日本ワクチン学会学術集会
  • Place of Presentation: 名鉄犬山ホテル（愛知県犬山市）
  • Year and Date: 2015-11-14
• [Presentation] インジェクタブル人工エラスチンゲルによる抗HIVペプチドのデポ製剤化 (2015)
  • Author(s): 浅井大輔、金本大成、寺久保繁美、Ashutosh Chilkoti、武永美津子、中島秀喜
  • Organizer: 第３７回日本バイオマテリアル学会大会
  • Place of Presentation: 京都テルサ（京都市南区）
  • Year and Date: 2015-11-09
• [Presentation] インジェクタブル人工エラスチンによる抗原デポ剤：破傷風トキソイドの徐放効果の解析 (2015)
  • Author(s): 浅井大輔、福田靖、諸熊一則、Ashutosh Chilkoti、柴山恵吾、中島秀喜
  • Organizer: 第３１回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-02
• [Presentation] ケミカルバイオロジー分子ツールの開発：ROCK2およびGRK2選択的ペプチド性基質 (2014)
  • Author(s): 浅井大輔、戸井田力、土谷享、村田正治、片山佳樹、姜貞勲、中島秀喜
  • Organizer: 第８７回日本生化学大会
  • Place of Presentation: 京都国際会館、京都市左京区
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Development of peptide-based compounds for cytotoxicity induction utilizing ubiquitous endogenous IgG (2014)
  • Author(s): Funamoto, D., Park, S., Mori, T., Asai, D., Kishimura, A., Sato, K., Yamaguchi, Y., and Katayama, Y
  • Organizer: The IUMRS International Conference in Asia 2014
  • Place of Presentation: Fukuoka University, Fukuoka
  • Year and Date: 2014-08-24 – 2014-08-30
• [Presentation] 新規KSP阻害剤の抗腫瘍効果に関する研究（第２報） (2014)
  • Author(s): 武永美津子、竹内智紀、都倉享恵、濱口明美、山本有貴、太田有紀、浅井大輔、中島秀喜、大石真也、藤井信孝
  • Organizer: 第３０回日本DDS学会学術集会
  • Place of Presentation: 慶応大学薬学部、東京都港区
  • Year and Date: 2014-07-30 – 2014-07-31
• [Presentation] 内在性のIgGにより細胞毒性を誘導できるペプチド性化合物の開発 (2014)
  • Author(s): 船本大起、パクサウン、森健、浅井大輔、岸村顕広、佐藤一紀、山口容子、片山佳樹
  • Organizer: 第６３回高分子学会年次大会
  • Place of Presentation: 名古屋国際会議場、名古屋市熱田区
  • Year and Date: 2014-05-28 – 2014-05-30
• [Remarks] 抗微生物薬の送達手法開発（聖マリアンナ医科大学 微生物学教室）
  • URL: http://www.marianna-u.ac.jp/microbiology/office/003334.html
• [Remarks] 抗微生物薬の送達手法開発（聖マリアンナ医科大学微生物学教室）
  • URL: http://www.marianna-u.ac.jp/microbiology/office/003334.html