A study of TCR-V・targeted antibody therapy against human T cell lymphoma

• Project/Area Number: 23659286
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Kagoshima University
• Principal Investigator: ARIMA Naomichi 鹿児島大学, 大学院・医歯学総合研究科, 教授 (30175997)
• Co-Investigator(Kenkyū-buntansha): ITO Yuji 鹿児島大学, 大学院・理工学研究科, 教授 (60223195)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 抗体療法 / TCR-Vβ / T細胞性リンパ腫 / 治療薬 / Ｔ細胞性腫瘍 / 成人Ｔ細胞白血病 / ファージデイスプレイ法 / scFv antibody / 分子標的療法 / 患者TCRに対する抗体療法

Research Abstract

Under admission of IRB, repertoire of TCRVb of leukemic cells derived from an ATL patient was demonstrated Vb2. Full length of TCR αand βwere separated from extracted RNA by 5’RACE method. TCRb expressing vector was established using lenti-virus bector system, and infected into Jurkat cells which expresses successfully trnsfected TCRβ2 protein. On the other hands, human anbibody heavy and light chain expressing phage library was constructed using normal health lymphocyte RNA. Using these two materials, we further study establishment of malignant T cell targeted antibody therapy.

Research Products

• [Journal Article] The bioassay- uided isolation of growth inhibitors of adult T-cell leukemia (ATL), from the Jamaican plant Hyptis verticillata, and NMRcharacterization of Hyptoside (2012)
  • Author(s): Hamada T, White Y, Nakashima M, Oiso Y, Fujita MJ, Okamura H, Iwagawa T, Arima N
  • Journal Title: Molecules Volume: 17 Pages: 9931-9938
  • Peer Reviewed
• [Journal Article] Recombinant human soluble thrombomodulin for the treatment of hepatic sinusoidal obstructivesyndrome postallogeneic hematopoietic (2012)
  • Author(s): Nakamura D, Yoshimitsu M, Kawada H, Inoue H, Kuroki T, Kaieda T, Fujino S, Hamada H, Suzuki S, Matsushita K, Uozumi K, Arima N
  • Journal Title: SCT.Bone Marrow Transplantation Volume: 47 Pages: 463-464
  • Peer Reviewed
• [Journal Article] High expression of SIRT1, a Longevity gene-encoded protein, and induction of apoptosis by its inhibition in adult T-cell leukemia cells (2012)
  • Author(s): Kozako T, Aikawa A, Shoji T, Fujimoto T, Yoshimitsu M, Shirasawa S, Tanaka H, Honda SI, Shimeno H, Arima N, Soeda S
  • Journal Title: Int J Cancer Volume: 131 Pages: 2044-2955
  • Peer Reviewed
• [Journal Article] Liposomes and nanotechnology in drug development: fous on oncotargets (2012)
  • Author(s): Kozako T, Arima N, Yoshinmitsu M, Honda S-I, Soeda S
  • Journal Title: Int J Nanomed Volume: 7 Pages: 4943-4951
  • Peer Reviewed
• [Journal Article] 多発性骨髄腫の最 新治療;骨髄腫腎や分子標的薬を含めて (2012)
  • Author(s): 川田英明、有馬直道
  • Journal Title: 日本腎臓学会誌 Volume: 第54巻第5号 Pages: 586-592
  • NAID: 10030965968
• [Journal Article] 成人T 細胞白血病・リンパ腫 (2012)
  • Author(s): 有馬直道
  • Journal Title: 今日の治療指針 医学書院 Pages: 586-588
• [Presentation] Establishment of a BCL2/MYC dual hit lymphoma (DHL) cell line from a patient with B cell lymphoma (2012)
  • Author(s): Arima N, Yoshimitsu M, Kawada H, Arai A, Nakamura D, Shiraishi M, Hamada H, Suzuki S, Matsushita K, Uozumi K, Arima N
  • Organizer: 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Kyoto
  • Year and Date: 2012-10-21
• [Presentation] Achieving clear status of recalcitrant psoriasis during low-dose dasatinib in a patient with CML (2012)
  • Author(s): Suzuki S, Uozumi K, Yoshimitsu M, Kawada H, Hamada H, Nakamura D, Arima N, Shiraishi M, Matsushita K, Arima N
  • Organizer: 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Kyoto
  • Year and Date: 2012-10-20
• [Presentation] A novel cytotoxic agent, 4-MTDND, induces apoptosis and overcomes multidrug resistance against ATLL (2012)
  • Author(s): Yoshimitsu M, White Y, Hamada T, Nakashima M, Hachiman M, Uozumi K, Furukawa T, Arima N
  • Organizer: 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Kyoto
  • Year and Date: 2012-10-20
• [Presentation] Establishment of an ATLL zenotransplant mouse model using the NOD/SCID/Jak3 null (NOJ) mouse (2012)
  • Author(s): Nakamura D, Yoshimitsu M, Niimoto J, Kuroki A, White Y, Uozumi K, Okada S, Arima N
  • Organizer: 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Kyoto
  • Year and Date: 2012-10-19
• [Presentation] POEMS 症候群に対する新規薬の効果 (2012)
  • Author(s): 新居亮彦,川田英明,林田真衣子,中村 大輔,吉満 誠,井上大栄,浜田平一郎,鈴木紳介,魚住公治,有馬直道
  • Organizer: 第109回日本内科学会講演会
  • Place of Presentation: 京都
  • Year and Date: 2012-04-13
• [Presentation] オリゴマンノース被覆リポソームによる効率的な HTLV-1 特異的細胞障害性 T 細胞の誘導 (2012)
  • Author(s): 小迫知弘、平田真哉、清水佳隆、占野廣司、添田秦司、有馬直道
  • Organizer: 第132 年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-28
• [Presentation] SIRT1 活性化剤による白血病細胞の増殖抑制効果に関する検討 (2012)
  • Author(s): 植村陽菜、小迫知弘、有馬直道、田中宏暁、本田伸一郎、添田秦司
  • Organizer: 第5回 HTLV 研究会
  • Place of Presentation: 東京
• [Patent(Industrial Property Rights)] 抗腫瘍剤及びその製造法 (2012)
  • Inventor(s): 有馬直道、濱田俊之、ホワイトヨハン
  • Industrial Property Rights Holder: 鹿児島大学
  • Filing Date: 2012-12-25
  • Overseas