A new strategy for antibody-therapy against infectious diseases and bacterial terrorism using lymphocyte-chip

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390286
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: University of Toyama
• Principal Investigator: MURAGUCHI Atsushi University of Toyama, 大学院・医学薬学研究部, 教授 (20174287)
• Co-Investigator(Kenkyū-buntansha): KISHI Hiroyuki 富山大学, 大学院・医学薬学研究部, 准教授 (60186210) ; OZAWA Tatsuhiko 富山大学, 大学院・医学薬学研究部, 助教 (10432105) ; KITAJIMA Isao 富山大学, 大学院・医学薬学研究部, 教授 (50214797) ; NIKAIDO Toshio 富山大学, 大学院・医学薬学研究部, 教授 (50180568)
• Project Period (FY): 2008 – 2010
• Keywords: リンパ球チップ / 抗体医療 / 抗体遺伝子

Research Abstract

We developed ISAAC (Immunospot assay for antibody-secreting cell) method that can detect antibody-secreting cells in a microwell using murine system. We then succeeded in generating high-quality human monoclonal antibodies for hepatitis B virus and influenza virus from vaccinated healthy volunteers using the ISAAC method in a very short time ; within one week. We further developed an in vitro assay system to examine the HBV-neutralizing activity of human anti-HBs antibodies and clarified the relationship between neutralizing activity of human mAbs and epitopes of HBs antigen.

Research Products

• [Journal Article] Generation of TRAIL-receptor 1-specific human monoclonal Ab by a combination of immunospot array assay on a chip and human Ab-producing mice. (2010)
  • Author(s): Jin A., Ozawa T., Tajiri K., Lin Z., Obata T., Ishida I., Kishi H., Muraguchi A.
  • Journal Title: Eur.J.Immunol. 40 Pages: 3591-3593
  • Peer Reviewed
• [Journal Article] Analysis of the epitope and neutralizing capacity of human monoclonal antibodies induced by hepatitis B vaccine. (2010)
  • Author(s): Tajiri K., Ozawa T., Jin A., Tokimitsu Y., Minemura M., Kishi H., Sugiyama T., Muraguchi A.
  • Journal Title: Antiviral.Res. 87 Pages: 40-49
  • Peer Reviewed
• [Journal Article] Post-translational modification of TRAIL receptor type 1 on various tumor cells and the susceptibility of tumors to TRAIL-induced apoptosis. (2010)
  • Author(s): Lin Z., Jin A., Ozawa T., Tajiri K., Obata T., Ishida I., Jin F., Kishi H., Muraguchi A.
  • Journal Title: Biochem.Biophys.Res.Commun. 395 Pages: 251-257
  • Peer Reviewed
• [Journal Article] A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. (2009)
  • Author(s): Jin A.-S., Ozawa T., Tajiri K., Obata T., Kondo S., Kinoshita K., Kadowaki S., Takahashi K., Sugiyama T., Kishi H., Muraguchi A.
  • Journal Title: Nat.Med. 15 Pages: 1088-1092
  • Peer Reviewed
• [Journal Article] Identification of antigen-specific B cells by concurrent monitoring of intracellular Ca^<2+> mobilization and antigen binding with microwell array chip system equipped with a CCD imager. (2009)
  • Author(s): Kinoshita K., Ozawa T., Tajiri K., Kadowaki S., Kishi H., Muraguchi A.
  • Journal Title: Cytometry Part A 75A Pages: 682-687
  • Peer Reviewed
• [Journal Article] SFMAC : A novel method for analyzing multiple parameters on lymphocytes with a single fluorophore in cell-microarray system. (2009)
  • Author(s): Tajiri K., Kishi H., Ozawa T., Sugiyama T., Muraguchi A.
  • Journal Title: Cytometry Part A 75A Pages: 282-288
  • Peer Reviewed
• [Journal Article] MAC-CCD system : a novel lymphocyte microwell-array chip system equipped with CCD scanner to generate human monoclonal antibodies against influenza virus. (2009)
  • Author(s): Ozawa T., Kinoshita K., Kadowaki S., Tajiri K., Kondo S., Honda R., Ikemoto M., Piao L.-X., Morisato A., Fukurotani K., Kishi H., Muraguchi A.
  • Journal Title: Lab on a Chip 9 Pages: 158-163
  • Peer Reviewed
• [Presentation] Characterization of human anti-influenza M2 antibody obtained from peripheral blood of vaccinated volunteer. (2011)
  • Author(s): Muraguchi A., Ozawa T., Jin A., Tajiri K., Takemoto M., Okuda T., Shiraki K., Kishi H.
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone, USA.
  • Year and Date: 20110206-20110211
• [Presentation] Isolation and characterization of a fully human monoclonal antibody against extracellular domain of matrix protein 2 of influenza A virus. (2010)
  • Author(s): Ozawa T., Jin A., Tajiri K., Takemoto M., Okuda T., Shiraki K., Kishi H., Muraguchi A.
  • Organizer: Cold Spring Harbor Conferences Asia
  • Place of Presentation: Suzhou, China.
  • Year and Date: 20101107-20101110
• [Presentation] Enhancement of TRAIL-induced apoptosis with novel TRAIL-receptor 1 specific human mAbs generated by Immunospot array assay on a chip. (2010)
  • Author(s): Jin A., Ozawa T., Tajiri K., Lin Z., Kishi H., Muraguchi A.
  • Organizer: Cold Spring Harbor Conferences Asia
  • Place of Presentation: Suzhou, China.
  • Year and Date: 20101107-20101110
• [Presentation] Enhancement of TRAIL-induced apoptosis with novel TRAIL-R1-specific human mAbs generated by immunospot array assay on a chip. (2010)
  • Author(s): Kishi H., Jin A., Ozawa T., Tajiri K., Lin Z., Obata T., Ishida I., Muraguchi A.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe.
  • Year and Date: 20100822-20100827
• [Presentation] Characterization of human anti-influenza M2 antibody obtained from peripheral blood of vaccinated volunteer. (2010)
  • Author(s): Ozawa T., Jin A., Tajiri K., Shiraki K., Kishi H., Muraguchi A.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe.
  • Year and Date: 20100822-20100827
• [Presentation] Detection of antigen-specific T-cell response on the single cell-basis with microwell array chip. (2010)
  • Author(s): Kishi H., Tajiri K., Hatakeyama S., Kobayashi E., Horii M., Jin A., Ozawa T., Muraguchi A.
  • Organizer: 4th Measuring Antigen-Specific Immune Response (MASIR) Conference
  • Place of Presentation: Mykonos, Greece.
  • Year and Date: 20100609-20100612
• [Presentation] A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. (2009)
  • Author(s): 小澤龍彦, 金艾順, 田尻和人, 小幡勤, 近藤佐千子, 木下耕史, 門脇慎一, 高橋和郎, 杉山敏郎, 岸裕幸, 村口篤
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. (2009)
  • Author(s): 金艾順, 小澤龍彦, 田尻和人, 岸裕幸, 村口篤
  • Organizer: IBC's 20th Annual International Conference Antibody Engineering
  • Place of Presentation: San Diego, USA.
  • Year and Date: 20091206-20091210
• [Presentation] 単一細胞レベルにおけるB細胞受容体シグナル解析 (2009)
  • Author(s): 岸裕幸, 小澤龍彦, 田尻和人, 村口篤
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] Isolation of human anti-influenza M2 antibody from peripheral blood of healthy volunteer. (2009)
  • Author(s): 小澤龍彦, 田尻和人, 金艾順, 岸裕幸, 村口篤
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. (2009)
  • Author(s): 金艾順, 小澤龍彦, 田尻和人, 岸裕幸, 村口篤
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] Extracellular loop domain of small (S)-HBsAg play a major role in preventing the infection of HBV : the result from omprehensive analysis of monoclonal antibodies obtained from S-HBsAg-vaccinated healthy individuals. (2009)
  • Author(s): Tajiri K., Ozawa T., Jin A.-S., Tokimitsu Y., Nakayama Y., Minemura M., Kishi H., Sugiyama T., Muraguchi A.
  • Organizer: The 8th JSH Single Topic Conference
  • Place of Presentation: Tokyo.
  • Year and Date: 20091121-20091122
• [Presentation] B-cell receptor signal analysis at single cell levels using a microwell-array chip. (2009)
  • Author(s): Kinoshita K., Kishi H., Fukurotani K., Honda R., Ozawa T., Tajiri K., Muraguchi A.
  • Organizer: Cold Spring Harbor Meeting
  • Place of Presentation: New York.
  • Year and Date: 20091111-20091114
• [Presentation] Microwell arrays for detecting single, antigen-specific B-lineage cells. (2008)
  • Author(s): 岸裕幸
  • Organizer: IBC's 19th Annual International Conference Antibody Engineering
  • Place of Presentation: San Diego.
  • Year and Date: 20081207-20081211
• [Presentation] マイクロウェルアレイチップを用いた抗原特異的T細胞の検出 (2008)
  • Author(s): 岸裕幸, 田尻和人, 小澤龍彦, 金艾順, 村口篤
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 20081201-20081203