Development of novel immunotherapy targeting leukemic stem cells.

• Project/Area Number: 26461453
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Keio University
• Principal Investigator: Matsushita Maiko 慶應義塾大学, 薬学部(芝共立), 准教授 (10327520)
• Co-Investigator(Kenkyū-buntansha): 服部 豊 慶應義塾大学, 薬学部(芝共立), 教授 (20189575) ; 河上 裕 慶應義塾大学, 医学部(信濃町), 教授 (50161287)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 白血病幹細胞 / がん抗原 / CTL / 脱メチル化剤 / T細胞 / 免疫療法 / エピジェネティクス

Outline of Final Research Achievements

Novel cancer antigen, CXorf48, was highly expressed in patients-derived leukemic stem cells. Cytotoxic T cells induced with HLA-A24-restricted epitope could recognize these leukemic stem cells from leukemic patients. We also found the correlation between existence of anti-CXorf48 CTL in peripheral blood of leukemic patients and their clinical courses.
Moreover, demethylating agent up-regulated expression of CXorf48 gene in leukemic cells, but not in normal blood cells, suggesting that combination of demethylating agent with immunotherapy might be effective. Therefore, immnotherapy targeting CXorf48 would be a promising treatment for leukemia by eradicating leukemic stem cells.

Research Products

• [Presentation] Immunogenicity of Novel Antigen Expressed in Leukemia Stem Cells. (2016)
  • Author(s): Ozawa K, Matsushita M, Yokoe S, Kanchi S, Uchiumi A, Ichikawa D, Matsuki E, Sakurai M, Karigane D, Kasahara H, Kawakami Y, Okamoto S, Hattori Y.
  • Organizer: The 5thJCA-AACR Joint Conference
  • Place of Presentation: 東京ベイ舞浜ホテル（千葉県浦安市）
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Presentation] Monitoring of immunity against leukemia stem cell in CML patients after cessation of TKI (2015)
  • Author(s): Matsushita M, Koji Ozawa, Kanchi S, Uchiumi A, Suzuki T, Ichikawa D, Matsuski E, Sakurai M, Karigane D, Nakajima H, Okamoto S, Hattori Y.
  • Organizer: 30th Annual Meeting of The Society for Immunotherapy of Cancer（SITC）
  • Place of Presentation: メリーランド州ナショナルハーバー （アメリカ合衆国）
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] イマチニブ投与中止後CML患者におけるがん幹細胞抗原特異的CTLの解析 (2015)
  • Author(s): 神地沙織、小澤光司、松下麻衣子、松木絵里、櫻井政寿、雁金大樹、市川大樹、岡本真一郎、服部豊
  • Organizer: 第７回血液疾患免疫療法研究会学術集会
  • Place of Presentation: 東京大学国際学術研究センター内 伊藤謝恩ホール（東京都文京区）
  • Year and Date: 2015-09-26
• [Presentation] 白血病幹細胞に発現する新規がん精巣抗原の同定 (2015)
  • Author(s): 小澤光司、松下麻衣子、中村美紀、鈴木拓真、市川大樹、塚本信夫、河上裕、服部豊
  • Organizer: 第12回日本免疫治療学研究会学術集会
  • Place of Presentation: 東京都 東京ガーデンパレス
  • Year and Date: 2015-02-28
• [Presentation] Identification of novel cancer-testis antigen expressed in leukemic stem cells of chronic myelogenous leukemia. (2014)
  • Author(s): Matsushita M, Nakamura M, Ichikawa D, Tsukamoto N, Kawakami Y, Hattori Y.
  • Organizer: ISEH 43rd Annual Scientific Meeting
  • Place of Presentation: カナダ モントリオール
  • Year and Date: 2014-08-21 – 2014-08-24