Development of novel therapy targeting lipid rafts in multiple myeloma

• Project/Area Number: 20591130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokushima
• Principal Investigator: OZAKI Shuji The University of Tokushima, 医学部・歯学部附属病院, 講師 (90314872)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 血液内科学 / 造血器腫瘍 / 多発性骨髄腫 / 脂質ラフト / モノクローナル抗体

Research Abstract

HM1.24 and HM1.27 are specifically overexpressed in myeloma cells and monoclonal antibodies specific to these antigens induced myeloma cell death by aggregation of lipid rafts. These antibodies mediated cell death and inhibited colony formation of myeloma stem cells. These results suggest that the antibody therapy targeting lipids rafts will be an important strategy for the treatment of multiple myeloma.

Research Products

• [Journal Article] Transient inflammatory reaction during lenalidomide plus reduced-dose dexamethasone therapy in two patients with relapsed multiple myeloma. (2011)
  • Author(s): Ozaki S, Harada T, Fujii S, Nakamura S, Miki H, Nakano A, Kagawa K, Takeuchi K, Abe M, Matsumoto T.
  • Journal Title: Int J Hematol 93 Pages: 257-259
  • Peer Reviewed
• [Journal Article] Transient inflammatory reaction during lenalidomide plus reduced-dose dexamethasone therapy in two patients with relapsed multiple myeloma. (2011)
  • Author(s): Ozaki S, et al.
  • Journal Title: Int J Hematol Volume: 93 Pages: 257-259
  • Peer Reviewed
• [Journal Article] Size-controlled synthesis, surface functionalization, and biological applications of thiol-organosilica particles. (2010)
  • Author(s): Nakamura M, Ozaki S, Abe M, Doi H, Matsumoto T, Ishimura K.
  • Journal Title: Colloids Surf B Biointerfaces 79 Pages: 19-26
  • Peer Reviewed
• [Journal Article] TGF-β inhibition restores terminal osteoblast differentiation to suppress myeloma growth. (2010)
  • Author(s): Takeuchi K, Abe M, Hiasa M, Oda A, Amou H, Kido S, Harada T, Tanaka O, Miki H, Nakamura S, Nakano A, Kagawa K, Yata K, Ozaki S, Matsumoto T.
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] TGF-β inhibition restores terminal osteoblast differentiation to suppress myeloma growth. (2010)
  • Author(s): Takeuchi K, et al.
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] Size-controlled synthesis, surface functionalization, and biological applications of thiol-organosilica particles. (2010)
  • Author(s): Nakamura M, et al.
  • Journal Title: Colloids Surf B Biointerfaces Volume: 79 Pages: 19-26
  • Peer Reviewed
• [Journal Article] GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme (TACE). (2009)
  • Author(s): Hiasa M, Abe M, Nakano A, Oda A, Amou H, Kido S, Takeuchi K, Kagawa K, Yata K, Hashimoto T, Ozaki S, Asaoka K, Tanaka E, Moriyama K, Matsumoto T.
  • Journal Title: Blood 114 Pages: 4517-4526
  • Peer Reviewed
• [Journal Article] A pharmacokinetic study evaluating the relationship between treatment efficacy and incidence of adverse events with thalidomide plasma concentrations in patients with refractory multiple myeloma. (2009)
  • Author(s): Kodama T, Abe M, lida S, Ozaki S, Sakai A, Sawamura M, Shimazaki C, Miyata A, Wakayama T, Murakami H.
  • Journal Title: Clin Lymphoma Myeloma 9 Pages: 154-159
  • Peer Reviewed
• [Journal Article] HM1. 24 (CD317) is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody. (2009)
  • Author(s): Wang W, Nishioka Y, Ozaki S, Jalili A, Abe S, Kakiuchi S, Kishuku M, Minakuchi K, Matsumoto T, Sone S.
  • Journal Title: Cancer Immunol Immunother 58 Pages: 967-976
  • Peer Reviewed
• [Journal Article] Marked improvement of platelet transfusion refractoriness after bortezomib therapy in multiple myeloma. (2009)
  • Author(s): Miki H, Ozaki S, Tanaka O, Lee E, Takimoto T, Watanabe H, Fujii S, Nakamura S, Kagawa K, Takeuchi K, Yata KI, Abe M, Kagami S, Matsumoto T.
  • Journal Title: Int J Hematol 89 Pages: 223-226
  • Peer Reviewed
• [Journal Article] Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-lalpha and MIP-lbeta production. (2009)
  • Author(s): Abe M, Hiura K, Ozaki S, Kido S, Matsumoto T.
  • Journal Title: J Bone Miner Metab 27 Pages: 16-23
  • Peer Reviewed
• [Journal Article] Chimeric and humanized anti-HM1.24 antibodies mediate antibody- dependent cellular cytotoxicity against lung cancer cells. (2009)
  • Author(s): Wang W, Nishioka Y, Ozaki S, Jalili A, Verma VK, Hanibuchi M, Abe S, Minakuchi K, Matsumoto T, Sone S.
  • Journal Title: Lung Cancer 63 Pages: 23-31
  • Peer Reviewed
• [Journal Article] Marked improvement of platelet transfusion refractoriness after bortezomib therapy in multiple myeloma (2009)
  • Author(s): Miki H, et al.
  • Journal Title: Int J Hematol 89 Pages: 223-226
  • Peer Reviewed
• [Journal Article] HM1.24(CD317)is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody (2009)
  • Author(s): Wang W, et al.
  • Journal Title: Cancer Immunol Immunother 58 Pages: 967-976
  • Peer Reviewed
• [Journal Article] GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme(TACE) (2009)
  • Author(s): Hiasa M, et al.
  • Journal Title: Blood 114 Pages: 4517-4526
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Ozaki S
  • Journal Title: Biologic therapies for multiple myeloma and plasma cell disorders. Emerging Protein Biotherapeutics(CRC Press) Pages: 267-279
• [Journal Article] Chimeric and humanized anti-HM1.24 antibodies mediate antibody-dependent cellular cytotoxicity against lung cancer cells. (2009)
  • Author(s): Wang w, et al.
  • Journal Title: Lung Cancer 63 Pages: 23-31
  • Peer Reviewed
• [Journal Article] Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-lalpha and MIP-1beta production. (2009)
  • Author(s): Abe M, et al.
  • Journal Title: J Bone Miner Metab 27 Pages: 16-23
  • Peer Reviewed
• [Journal Article] Interferon-alpha enhances CD317 expression and the antitumor activity of anti-CD317 monoclonal antibody in renal cell carcinoma xenograft models. (2008)
  • Author(s): Kawai S, Azuma Y, Fujii E, Furugaki K, Ozaki S, Matsumoto T, Kosaka M, Yamada-Okabe H.
  • Journal Title: Cancer Sci 99 Pages: 2461-2466
  • Peer Reviewed
• [Journal Article] Interferon-alpha enhances CD317 expression and the antitumor activity of anti-CD317 monoclonal antibody in renal cell carcinoma xenograftmodels. (2008)
  • Author(s): Kawai S, et al.
  • Journal Title: Cancer Sci 99 Pages: 2461-2466
  • Peer Reviewed
• [Presentation] HLA class Iに特異的なsingle-chain Fv diabodyは骨髄腫細胞のside population分画に傷害を及ぼす (2010)
  • Author(s): 池亀彰茂, 尾崎修治, 辻大輔, 原田武志, 中村信元, 三木浩和, 中野綾子, 賀川久美子, 竹内恭子, 矢田健一郎, 安倍正博, 伊藤孝司, 松本俊夫
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] HLA class I-specific single-chain Fv diabody eradicates the side population fraction of myeloma cells (2010)
  • Author(s): 池亀彰茂, ほか
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Presentation] 骨髄腫細胞のside populationを標的としたHLA class Iに特異的なscFv diabodyの抗腫瘍効果 (2009)
  • Author(s): 池亀彰茂, ほか
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-10-23
• [Presentation] A recombinant HLA class I-specific single-chain Fv diabody can target cancer stem cell-like side population cells in multiple myeloma. (2009)
  • Author(s): Akishige Ikegame, Shuji Ozaki, Daisuke Tsuji, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Ayako Nakano, Kumiko Kagawa, Kyoko Takeuchi, Ken-ichiro Yata, Masahiro Abe, Kohji Itoh, Toshio Matsumoto.
  • Organizer: 51^<th> Annual Meeting of the American Society of Hematology
  • Place of Presentation: New Orleans, Louisiana, USA
• [Presentation] 骨髄腫細胞のside populationを標的としたHLA class Iに特異的なscFv diabodyの抗腫瘍効果 (2009)
  • Author(s): 池亀彰茂, 尾崎修治, 辻大輔, 原田武志, 中村信元, 三木浩和, 中野綾子, 賀川久美子, 竹内恭子, 矢田健一郎, 安倍正博, 伊藤孝司, 松本俊夫
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Spicamycin誘導体であるKRN5500は骨髄腫細胞と破骨細胞の増殖を抑制し, 抗腫瘍効果を発揮する (2008)
  • Author(s): 三木浩和, ほか
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-10-12
• [Presentation] KRN5500, a spicamycin derivative, exerts anti-myeloma effects through impairing both myeloma cells and osteoclasts. (2008)
  • Author(s): Hirokazu Miki, Shuji Ozaki, Osamu Tanaka, Shingen Nakamura, Ayako Nakano, Kumiko Kagawa, Kyoko Takeuchi, Ken-ichiro Yata, Masahiro Abe, Toshio Matsumoto.
  • Organizer: 50^<th> Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Spicamycin誘導体KRN5500は骨髄腫細胞とともに破骨細胞の生存を抑制し,抗腫瘍効果を発揮する (2008)
  • Author(s): 三木浩和, 尾崎修治, 田中修, 藤井志朗, 中村信元, 賀川久美子, 竹内恭子, 坂井晃, 矢田健一郎, 安倍正博, 松本俊夫
  • Organizer: 第70回 日本血液学会総会
  • Place of Presentation: 国立京都国際会館
• [Book] Emerging Protein Biotherapeutics.(Biologic therapies for multiple myeloma and plasma cell disorders.) (2009)
  • Author(s): Ozaki S.
  • Publisher: Editor Iqbal S. Grewal, CRC Press, Boca Raton, FL, USA