Development of a novel therapy against refractory leukemia and lymphoma by using genetically-modified natural killer cells

• Project/Area Number: 18790706
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Niigata University
• Principal Investigator: IMAI Chihaya Niigata University, 医歯学系, 助教 (90419284)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: NK細胞 / 遺伝子導入 / 細胞療法 / chimeric receptor / 白血病 / リンパ腫 / IL-2 / 造血幹細胞移植 / Chimeric receptor

Research Abstract

従来遺伝子導入が困難とされてきたヒトNatural Killer (NK)細胞の、抗がん治療の上で有用な遺伝子改変について検討した。NK 細胞にリンパ球増殖因子であるIL-2 遺伝子を導入したところ、NK 細胞の生存促進と抗腫瘍効果の向上が示された。さらに、B リンパ性腫瘍特異的キメラ型受容体遺伝子、IL-2 遺伝子、マーカー遺伝子GFP を組み込んだ治療用ベクターを試作した。この3遺伝子を同時発現するベクターの実用化には、高い効率のパッケージング技術の確立が必要と考えられた。

Research Products

• [Journal Article] Replicative potential of human natural killer cells (2009)
  • Author(s): Fujisaki H, Kakuda H, Imai C, Mullighan CG, Campana D
  • Journal Title: Br J Haematol
  • Peer Reviewed
• [Journal Article] Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy (2009)
  • Author(s): Fujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T, Eldridge P, Leung WH, Campana D
  • Journal Title: Cancer Res
  • Peer Reviewed
• [Journal Article] Juvenile myelomonocytic leukemia with less aggressive clinical course and KRAS mutation (2008)
  • Author(s): Imamura M, Imai C, Takachi T, Nemoto T, Tanaka A, Uchiyama M
  • Journal Title: Pediatr Blood Cancer 51 Pages: 569-569
  • Peer Reviewed
• [Journal Article] Juvenile myelomonocytic leukemia with less aggressive clinical course and KRAS mutation (2008)
  • Author(s): Imamura M, Imai C, et.al.
  • Journal Title: Padiatric Blood and Cancer 51(4) Pages: 569-569
  • Peer Reviewed
• [Journal Article] 小児白血病における最近の話題 (2008)
  • Author(s): 今井千速
  • Journal Title: 新潟県小児科医会会報 41 Pages: 31-34
• [Journal Article] Enhancement of the anti-leukemic activity of cytokine induced killer cells with an anti-CD19 chimeric receptor delivering a 4-1BB-ζ activatin (2007)
  • Author(s): Marin V,Kakuda H,Dander E,Imai C,Campana D,Biondi A,D'Amico G
  • Journal Title: Experimental Hematology 35 Pages: 1388-97
  • Peer Reviewed
• [Journal Article] Genetic Modification of Natural Killer Cells for Leukemia Therapies (2007)
  • Author(s): Imai C, Kakuda H, Fujisaki H, Iwamoto S, Campana D
  • Journal Title: Anti-Inflammatory Anti-Allergy Agents in Medicinal Chemistry 6 Pages: 101-108
  • Peer Reviewed
• [Journal Article] Genetic Modification of Natural Killer Cells for Leukemia Therapies. (2007)
  • Author(s): Chihaya Imai, et. al.
  • Journal Title: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 6 Pages: 101-108
  • Peer Reviewed
• [Journal Article] Enhancement of the anti-leukemic activity of cytokine induced killer cells with an anti-CD19 chimeric receptor delivering a 4-1BBζactivating signal (2007)
  • Author(s): Mari V, Imai C, et. al.
  • Journal Title: Experimental Hematology 35 Pages: 1388-1397
  • Peer Reviewed
• [Journal Article] Synthetic messenger RNA as a tool for gene therapy (2006)
  • Author(s): Rabinovich PM, Komarovskaya ME, Ye ZJ, Imai C, Campana D, Bahceci E, Weissman SM
  • Journal Title: Hum. Gene Ther 17 Pages: 1027-35
  • Peer Reviewed
• [Journal Article] 抗CD19 レセプターを導入したNK 細胞による白血病・リンパ腫の治療 (2006)
  • Author(s): 今井千速
  • Journal Title: 臨床免疫 45 Pages: 503-510
• [Journal Article] 遺伝子操作により誘導される抗白血病NK細胞 (2006)
  • Author(s): 今井千速
  • Journal Title: 血液・腫瘍科 52 Pages: 414-423
• [Journal Article] 遺伝子操作により誘導される抗白血病NK細胞 (2006)
  • Author(s): 今井 千速
  • Journal Title: 血液・腫瘍科 52 (4) Pages: 414-423
• [Journal Article] 抗CD19レセプターを導入したNK細胞による白血病・リンパ腫の治療 (2006)
  • Author(s): 今井 千速
  • Journal Title: 臨床免疫 45 (5) Pages: 503-510
• [Presentation] Interleukin-2 gene transduction in human natural killer cells augments their survival and anti-leukemic capacity (publication only) (2008)
  • Author(s): Chihaya Imai, et al
  • Organizer: 50th American Society of Hematology Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] IL-2 遺伝子導入NK 細胞の生存促進と抗腫瘍効果の持続的発現 (2008)
  • Author(s): 今井千速
  • Organizer: 第67回日本血液学会
  • Place of Presentation: 京都
• [Presentation] Interleukin-2 gene transduction in human natural killer cells augments their surval and anti-leukemic capacity(publication only) (2008)
  • Author(s): Imai C, et.al.
  • Organizer: The American Society of Hematology 50th Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] Simultaneous Use of Histone Deacetylase Inhibitor Valproic Acid Potentiates Natural Killer Cell Cytotoxicity Against T-Lineage Acute Lymphoblastic Leukemia(publication only) (2008)
  • Author(s): Takachi T, Imai C, et.al.
  • Organizer: The American Society of Hematology 50th Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] IL-2遺伝子導入NK細胞の生存促進と抗腫瘍効果の持続的発現(優秀ポスター演題に選定) (2008)
  • Author(s): 今井千速, ら
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都市
• [Presentation] Activated T Cell-Mediated Immunotherapy with a Chimeric Receptor against CD38 in B-Cell Malignancies (2007)
  • Author(s): Mihara K, Imai C, et. al.
  • Organizer: American Society of Hematology
  • Place of Presentation: 米国ジョージア州アトランタ
  • Year and Date: 2007-12-09