Development of trifunctional antibodies in multiple myeloma

• Project/Area Number: 24591402
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: YASUI Hiroshi 東京大学, 医科学研究所, 特任講師 (40448593)
• Co-Investigator(Kenkyū-buntansha): ISHIDA Tadao 札幌医科大学, 医学部, 准教授 (20305220)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 多発性骨髄腫 / 抗体医薬 / 橋渡し研究 / 三重特異性抗体 / がん免疫療法 / 改変抗体 / 免疫細胞

Outline of Final Research Achievements

The trifunctional antibody can bind specifically to tumor antigens and the T-cell antigen CD3 via each of the Fab-fragments as well as to macrophages via its Fc-fragment. We have developed a trifunctional antibody, which binds to CD3 and antigen A expressed on the surface of multiple myeloma cells. Such binding results in antibody-dependent cell-mediated cytotoxicity against myeloma cells as well as antitumor activity in human myeloma mouse model. We plan on acquiring the intellectual property rights as well as the university-industry research collaboration in order to put this finding to the practical use as an anti-myeloma drug.

Research Products

• [Journal Article] High Level of Serum Soluble Interleukin-2 Receptor at Transplantation Predicts Poor Outcome of Allogeneic Stem Cell Transplantation for Adult T Cell Leukemia. (2014)
  • Author(s): Shigematsu A, Kobayashi N, Yasui H, Shindo M, Kakinoki Y, Koda K, Iyama S, Kuroda H, Tsutsumi Y, Imamura M, Teshima T.
  • Journal Title: Biol Blood Marrow Transplant Volume: － Issue: 6 Pages: 801-805
  • DOI: 10.1016/j.bbmt.2014.02.014
  • NAID: 120005455889
  • Peer Reviewed / Open Access
• [Journal Article] Epstein-Barr virus-infected cells in IgG4-related lymphadenopathy with comparison to extranodal IgG4-related disease (2014)
  • Author(s): Takeuchi M, Sato Y, Yasui H, Ozawa H, Ohno K, Takata K, Iwaki N, Orita Y, Asano N, Nakamura S, Swerdlow SH, Yoshino T
  • Journal Title: Am J Surg Pathol Volume: 38 Pages: 946-955
  • Peer Reviewed
• [Journal Article] DNA synthesis inhibitors for the treatment of gastrointestinal cancer (2014)
  • Author(s): Yasui H, Tsurita G, Imai K
  • Journal Title: Expert Opin Pharmacother Volume: 15 Issue: 16 Pages: 2361-2372
  • DOI: 10.1517/14656566.2014.958074
  • Peer Reviewed
• [Journal Article] Long-term survey of survival time, histological transformation, and secondary malignancies in Japanese patients with advanced-stage follicular lymphoma in the rituximab era: Hokkaido Hematology Study Group (2014)
  • Author(s): Hirayama Y, Ishitani K, Ota S, Kurosawa M, Kondo T, Takimoto R, Mori A, Sakai H, Torimoto Y, Yamamoto S, Sato K, Iwasaki H, Kohda K, Ishida T, Kakinoki Y, Fukuhara T, Kato J
  • Journal Title: Int J Hematol Volume: 100 Issue: 3 Pages: 281-289
  • DOI: 10.1007/s12185-014-1629-4
  • Peer Reviewed
• [Journal Article] Autologous stem cell transplantation for AL amyloidosis: adjustment of melphalan dose by factors including BNP (2014)
  • Author(s): Hayashi T, Ikeda H, Igarashi T, Maruyama Y, Aoki Y, Nojima M, Ishida T, Shinomura Y
  • Journal Title: Int J Hematol Volume: 100 Issue: 6 Pages: 554-558
  • DOI: 10.1007/s12185-014-1680-1
  • Peer Reviewed
• [Journal Article] Epstein-Barr Virus-infected Cells in IgG4-related Lymphadenopathy With Comparison With Extranodal IgG4-related Disease. (2014)
  • Author(s): Takeuchi M, Sato Y, Yasui H, Ozawa H, Ohno K, Takata K, Gion Y, Orita Y, Tachibana T, Itoh T, Asano N, Nakamura S, Swerdlow SH, Yoshino T.
  • Journal Title: Am J Surg Pathol. Volume: － Issue: 7 Pages: 946-955
  • DOI: 10.1097/pas.0000000000000206
  • Peer Reviewed
• [Journal Article] Coadministration of tenofovir decreased atazanavir plasma concentration after unilateral nephrectomy. (2013)
  • Author(s): Kunimoto Y, Yasui H, Touda N, Okazaki M, Nakata H, Noda N, Ikeda H, Hayashi T, Takahashi S, Shinomura Y, Ishida T, Miyamoto A.
  • Journal Title: J Infect Chemother. Volume: 19 Issue: 4 Pages: 750-3
  • DOI: 10.1007/s10156-012-0488-2
  • NAID: 10031194406
  • Peer Reviewed
• [Journal Article] Model of translational cancer research in multiple myeloma. (2012)
  • Author(s): Yasui H, et al.
  • Journal Title: Cancer Sci. Volume: 103 Pages: 1907-1912
  • Peer Reviewed
• [Journal Article] Genomic vulnerability to LINE-1 hypermethylation is a potential determinant of the clinicogenetic features of multiple myeloma. (2012)
  • Author(s): Aoki Y, Nojima M, Suzuki H, Yasui H, Maruyama R, Yamamoto E, Ashida M, Itagaki M, Asaoku H, Ikeda H, Hayashi T, Imai K, Mori M, Tokino T, Ishida T, Toyota M, Shinomura Y
  • Journal Title: Genome Medicine Volume: (印刷中) Issue: 12
  • DOI: 10.1186/gm402
  • Peer Reviewed
• [Presentation] 教育講演42「骨髄腫の染色体異常とclonal evolution」 (2014)
  • Author(s): 石田 禎夫
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-02
  • Invited
• [Presentation] トランスレーショナルリサーチの意義と展望
  • Author(s): 安井寛
  • Organizer: 第23回日本臨床化学会北海道支部例会
  • Place of Presentation: 札幌市
  • Invited
• [Presentation] 多発性骨髄腫におけるLINE-1 異常低メチル化と臨床遺伝子学的特徴の相関
  • Author(s): 野島正寛、青木由佳、安井 寛、丸山玲緒、山本英一郎、麻奥英毅、時野隆至、長村文孝、石田禎夫、今井浩三、篠村恭久、鈴木拓
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜市
• [Presentation] Hypomethylation of endogenous retrotransposons is correlated with frequent chromosomal deletions and poor prognosis in multiple myeloma
  • Author(s): Yasui H, et al.
  • Organizer: 17th Congress of the European Hematology Association
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] Hypomethylation of Retrotransposons is Correlated with Malignant Levels, Frequency of Chromosomal Aberrations, and Poor Prognosis in Multiple Myeloma.
  • Author(s): Yasui H, et al.
  • Organizer: JSH International Symposium 2012
  • Place of Presentation: Kawagoe, Japan
• [Presentation] Role of Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia in an HTLV-1 Non-Endemic Area of Japan
  • Author(s): Shigematsu A, et al.
  • Organizer: 54th ASH Annual Meeting
  • Place of Presentation: Atlanta, USA
• [Presentation] 多発性骨髄腫におけるDNAメチロームと遺伝子発現・染色体異常との関連
  • Author(s): 安井 寛ら
  • Organizer: 第37回日本骨髄腫学会学術集会
  • Place of Presentation: 京都
• [Presentation] 多発性骨髄腫におけるゲノム・エピゲノム解析とトランスレーショナルリサーチの試み
  • Author(s): 安井 寛ら
  • Organizer: 第63回日本電気泳動学会学術集会
  • Place of Presentation: 沖縄県宜野湾市
  • Invited
• [Presentation] 多発性骨髄腫における基礎研究の進歩と臨床応用
  • Author(s): 安井 寛ら
  • Organizer: 第54回日本血液学会秋季北海道地方会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] A model of Translational Cancer Research in Multiple Myeloma
  • Author(s): Yasui H, et al.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 多発性骨髄腫の発生におけるDNAメチロームの意義：MBDシーケンシング法によるアプローチ
  • Author(s): 野島 正寛ら
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 多発性骨髄腫における骨髄ストローマ細胞と単球との相互作用の解析
  • Author(s): 池田 博 ら
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Study of FLC and PIC in immunoglobulin light chain amyloidosis
  • Author(s): Yasui H, et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Book] 抗体医薬 PHARM TECH JAPAN臨時増刊号「日本DDS学会創立30周年記念誌」 (2015)
  • Author(s): 安井 寛、今井浩三
  • Total Pages: 282
  • Publisher: 株式会社じほう
• [Book] 多発性骨髄腫に対する新たな抗体医薬開発の現状 血液内科 特集「新規ターゲットおよび医薬品による血液がん治療の新たな展開」 (2015)
  • Author(s): 安井 寛、石田禎夫
  • Total Pages: 284
  • Publisher: 科学評論社
• [Book] Multiple Myeloma: Risk Factors, Diagnosis and Treatments (The Role of DNA Methylation in the Genetics and Epigenetics of Multiple Myeloma) (2014)
  • Author(s): Yasui H, Ishida T, Imai K
  • Total Pages: 249
  • Publisher: Nova Science Publishers
• [Book] 核酸を用いるＤＤＳ治療の現状と将来 医薬ジャーナル 特集「Drug delivery system (DDS) の最新展望」 (2014)
  • Author(s): 安井 寛
  • Total Pages: 200
  • Publisher: 医薬ジャーナル社
• [Book] 抗がん細胞抗体－その開発のあゆみとがん抗体療法の新たな可能性 実験医学増刊「腫瘍免疫学とがん免疫療法」 (2013)
  • Author(s): 安井 寛、今井浩三
  • Total Pages: 230
  • Publisher: 羊土社
• [Book] 抗体を用いたターゲッティング 応用が拡がるDDS 人体環境から農業・家電まで- (2013)
  • Author(s): 安井 寛, 今井浩三
  • Total Pages: 578
  • Publisher: エヌ・ティー・エヌ
• [Book] 造血器腫瘍とエピジェティクス-治療への応用と新たな展開- (2012)
  • Author(s): 安井 寛、石田禎夫 ら
  • Total Pages: 251
  • Publisher: 医薬ジャーナル社