Development and analysis of human monoclonal antibodies derived from patients with cancer

• Project/Area Number: 23650607
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor immunology
• Research Institution: University of Toyama
• Principal Investigator: ISOBE Masaharu 富山大学, 大学院・理工学研究部, 教授 (70211050)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヒトモノクローナル抗体 / 免疫学 / 癌 / MAGrahd法 / がん細胞 / 腫瘍マーカー / 抗体療法

Research Abstract

It has been known that the elevation of autoantibodies can frequently be observed in patients with cancer along with its progression. Among those some are potentially useful for the development of therapeutic or diagnostic antibodies for cancer. Recent development of our high-throughput isolation system of human monoclonal antibodies enabled us for the construction of antibody libraries from cancer patients derived antibody-producing single cells. The binding specificity of each antibody was examined by staining the cancer tissue from the same patient. After extensive screening we have succeeded in isolation of multiple antibodies that recognize cancer cells.

Research Products

• [Journal Article] Reduced Level of the BCL11B Protein Is Associated with Adult T-Cell Leukemia/Lymphoma (2013)
  • Author(s): Kurosawa, N., Fujimoto, R., Ozawa, T., Itoyama, T., Sadamori, N., and Isobe, M.
  • Journal Title: PloS one 8
• [Journal Article] Reduced Level of the BCL11B Protein Is Associated with Adult T-Cell Leukemia/Lymphoma (2013)
  • Author(s): Kurosawa, N.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e55147-e55147
  • DOI: 10.1371/journal.pone.0055147
  • Peer Reviewed
• [Journal Article] Rapid production of antigen-specific monoclonal antibodies from a variety of animals (2012)
  • Author(s): Kurosawa, N., Yoshioka, M., Fujimoto, R., Yamagishi, F., and Isobe, M.
  • Journal Title: BMC biology Volume: 10 Pages: 80-80
• [Journal Article] HELIOS-BCL11B fusion gene involvement in a t(2;14)(q34;q32) in an adult T-cell leukemia patient (2012)
  • Author(s): Fujimoto, R., Ozawa, T., Itoyama, T., Sadamori, N., Kurosawa, N., and Isobe, M.
  • Journal Title: Cancer genetics Volume: 205 Pages: 356-364
• [Journal Article] HELIOS-BCL11B fusion gene involvement in a t(2;14)(q34;q32) in an adult T-cell leukemia patient (2012)
  • Author(s): Fujimoto, R.
  • Journal Title: Cancer Genet Volume: 205 Issue: 7-8 Pages: 356-364
  • DOI: 10.1016/j.cancergen.2012.04.006
  • Peer Reviewed
• [Journal Article] Rapid production of antigen-specific monoclonal antibodies from a variety of animals (2012)
  • Author(s): Kurosawa, N.
  • Journal Title: BMC Biol Volume: 10 Issue: 1 Pages: 80-80
  • DOI: 10.1186/1741-7007-10-80
  • Peer Reviewed
• [Journal Article] Target-selective joint polymerase chain reaction: a robust and rapid method for high-throughput production of recombinant monoclonal antibodies from single cells (2011)
  • Author(s): Yoshioka, M., Kurosawa, N., and Isobe, M.
  • Journal Title: BMC biotechnology Volume: 11 Pages: 75-75
• [Journal Article] Target-selective homologous recombination cloning for high-throughput generation of monoclonal antibodies from single plasma cells (2011)
  • Author(s): Kurosawa, N., Yoshioka, M., and Isobe, M.
  • Journal Title: BMC biotechnology Volume: 11 Pages: 39-39
• [Journal Article] Target-selective homologous recombination cloning for high-throughput generation of monoclonal antibodies from single plasma cells. (2011)
  • Author(s): Nobuyuki Kurosawa, Megumi Yoshioka and Masaharu Isobe
  • Journal Title: BMC Biotechnology Volume: 11 Issue: 1 Pages: 39-39
  • DOI: 10.1186/1472-6750-11-39
  • Peer Reviewed
• [Journal Article] Target-selective joint polymerase chain reaction: a robust and rapid method for high-throughput production of recombinant monoclonal antibodies from single cells. (2011)
  • Author(s): Megumi Yoshioka, Nobuyuki Kurosawa and Masaharu Isobe
  • Journal Title: BMC Biotechnology Volume: 11 Issue: 1 Pages: 75-75
  • DOI: 10.1186/1472-6750-11-75
  • Peer Reviewed
• [Presentation] モルモット抗体可変領域遺伝子レパートリーの解析 (Analysis of immunoglobulin variable gene repertoire from the guinea pig.) (2012)
  • Author(s): 吉岡 めぐみ, 成瀬 輝芳, 黒澤 信幸, 磯部 正治
  • Organizer: 5回日本生化学会大会
  • Year and Date: 2012-12-16
• [Presentation] 様々な動物からの迅速な抗原特異的モノクローナル抗体作製法の開発 (Rapid production of antigen-specific monoclonal antibodies from a variety of animals.) (2012)
  • Author(s): 黒澤信幸, 吉岡 めぐみ, 藤本 理加, 磯部 正治
  • Organizer: 第85回日本生化学会大会
  • Year and Date: 2012-12-16
• [Presentation] Antigen-specific plasma/plasmablast cells identification from a variety of animals for the production of monoclonal antibodies. (2012)
  • Author(s): Nobuyuki Kurosawa , Megumi Yoshioka, Rika Fujimoto and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2012-12-03
• [Presentation] BCLL11B蛋白質発現減少は成人T細胞白血病の発症に関与する (2012)
  • Author(s): 黒澤 信幸, 藤本 理加, 磯部 正治
  • Organizer: 第71回日本癌学会学術総会
  • Year and Date: 2012-09-19
• [Presentation] Semi-Automatic Cloning and Expression of Immunoglobulin Genes from Single-Plasma Cells for High-Throughput Generation of Monoclonal Antibodies (2012)
  • Author(s): Masaharu Isobe
  • Organizer: PEP TALK The Protein Science Week PIPELINE4
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2012-01-09
• [Presentation] Semi-Automatic Cloning and Expression of Immunoglobulin Genes from Single- Plasma Cells for High-Throughput Generation of Monoclonal Antibodies. (2012)
  • Author(s): Masaharu Isobe
  • Organizer: PEP TALK The Protein Science Week PIPELINE4(招待講演)
  • Place of Presentation: San Diego, CA USA
• [Presentation] TS-jPCR 法を用いた単一細胞からのハイスループットな組換えモノクローナル抗体作製法の開発 (Target Selective-joint Polymerase Chain Reaction for High-throughput Generation of Recombinant Monoclonal Antibodies from Single Cells) (2011)
  • Author(s): San Diego, CA USA
  • Organizer: 第34回日本分子生物学会年会
  • Year and Date: 2011-12-12
• [Presentation] Magnetic-beads Reaction through Arrayed Hanging-Drops (MAGrahd) for high-throughput amplification of immunoglobulin genes from single B cells (2011)
  • Author(s): Nobuyuki Kurosawa, Megumi Yoshioka and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2011-12-04
• [Presentation] Target-selective homologous recombination cloning (TS-HR) for high-throughput generation of monoclonal antibodies from single plasma cells (2011)
  • Author(s): Rika Fujimoto, Megumi Yoshioka, Nobuyuki Kurosawa and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2011-12-04
• [Presentation] Target-selective joint polymerase chain reaction (TS-jPCR): A robust and rapid method for high-throughput production of recombinant monoclonal antibodies from single cells (2011)
  • Author(s): Megumi Yoshioka, Nobuyuki Kurosawa and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2011-12-04
• [Presentation] A robust and rapid system for high-throughput generation of recombinant monoclonal antibodies from a variety of species. (2011)
  • Author(s): Masaharu Isobe, Megumi Yoshioka, Rika Fujimoto and Nobuyuki Kurosawa
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2011-12-03
• [Presentation] 単一細胞からのハイスループットな抗体遺伝子/T細胞受容体遺伝子のクローニング及び発現システムの開発(High throughput cloning and expression of immunoglobulin genes/T-cell receptor genes from single cells.) (2011)
  • Author(s): 吉岡 めぐみ, 黒澤 信幸, 磯部 正治
  • Organizer: 第84回日本生化学会大会
  • Year and Date: 2011-09-23
• [Presentation] 単一細胞からのハイスループットな抗体遺伝子/Ｔ細胞受容体遺伝子のクローニング及び発現システムの開発(High throughput cloning and expression of immunoglobulin genes/T-cell receptor genes from single cells.) (2011)
  • Author(s): 吉岡 めぐみ,黒澤 信幸,磯部 正治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Magnetic-beads Reaction through Arrayed Hanging-Drops (MAGrahd) for high-throughput amplification of immunoglobulin genes from single B cells. (2011)
  • Author(s): Nobuyuki Kurosawa, Megumi Yoshioka and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
• [Presentation] Target-selective homologous recombination cloning (TS-HR) for high- throughput generation of monoclonal antibodies from single plasma cells. (2011)
  • Author(s): Rika Fujimoto, Megumi Yoshioka, Nobuyuki Kurosawa and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
• [Presentation] Target-selective joint polymerase chain reaction (TS-jPCR): A robust and rapid method for high-throughput production of recombinant monoclonal antibodies from single cells. (2011)
  • Author(s): Megumi Yoshioka, Nobuyuki Kurosawa and Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
• [Presentation] TS-jPCR法を用いた単一細胞からのハイスループットな組換えモノクローナル抗体作製法の開発(Target Selective-joint Polymerase Chain Reaction for High-throughput Generation of Recombinant Monoclonal Antibodies from Single Cells) (2011)
  • Author(s): 吉岡 めぐみ,黒澤 信幸,磯部 正治
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] BCLL11B蛋白質発現減少は成人T細胞白血病の発症に関与する
  • Author(s): 黒澤 信幸
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌
• [Presentation] A robust and rapid system for high-throughput generation of recombinant monoclonal antibodies from a variety of species.
  • Author(s): Masaharu Isobe
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
• [Presentation] Antigen-specific plasma/plasmablast cells identification from a variety of animals for the production of monoclonal antibodies.
  • Author(s): Nobuyuki Kurosawa
  • Organizer: Antibody Engineering
  • Place of Presentation: San Diego, CA USA
• [Presentation] モルモット抗体可変領域遺伝子レパートリーの解析 (Analysis of immunoglobulin variable gene repertoire from the guinea pig.)
  • Author(s): 吉岡 めぐみ
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 様々な動物からの迅速な抗原特異的モノクローナル抗体作製法の開発 (Rapid production of antigen-specific monoclonal antibodies from a variety of animals.)
  • Author(s): 黒澤 信幸
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場
• [Patent(Industrial Property Rights)] 反応治具及び反応方法、並びにcDNA合成方法 (2013)
  • Inventor(s): 磯部正治、黒澤信幸
  • Industrial Property Rights Holder: 立大学法人富山大学
  • Acquisition Date: 2013-04-12
• [Patent(Industrial Property Rights)] 形質細胞または形質芽細胞の選択方法,目的抗原特異的な抗体の製造方法,新規モノクローナル抗体 (2012)
  • Inventor(s): 黒澤信幸、磯部正治
  • Industrial Property Rights Holder: 国立大学法人富山大学
  • Filing Date: 2012-03-28
  • Overseas
• [Patent(Industrial Property Rights)] 形質細胞または形質芽細胞の選択方法，目的抗原特異的な抗体の製造方法，新規モノクローナル抗体 (2012)
  • Inventor(s): 黒澤信幸、磯部正治
  • Industrial Property Rights Holder: 国立大学法人富山大学
  • Filing Date: 2012
  • Overseas