Development research on immuno-gene therapy for malignant B-cell lymphoma

• Project/Area Number: 22700923
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Clinical oncology
• Research Institution: Jichi Medical University
• Principal Investigator: TSUKAHARA Tomonori 自治医科大学, 医学部, 助教 (10362120)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 悪性リンパ腫 / T細胞 / 腫瘍標的化 / 遺伝子治療

Research Abstract

For the treatment of refractory malignant B-cell lymphoma(B-cell non-Hodgkin lymphoma), we conducted experiments to develop an adoptive immuno-gene therapy using T-cells expressing a CAR(chimeric antigen receptor) targeting CD19.We demonstrated that genetically engineered T-cells efficiently lyzed CD19-positive B-cell lymphoma in vitro and in a mouse xenograft model. These results indicate that functional engineered T-cells would be effective for the treatment of refractory B-cell non-Hodgkin lymphoma.

Research Products

• [Journal Article] Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats (2012)
  • Author(s): Ogura M, Urabe M, Akimoto T, Onishi A, Ito C, Ito T, Tsukahara T, Mizukami H, Kume A, Muto S, Kusano E, and Ozawa K.
  • Journal Title: Gene Ther Volume: 19巻 Issue: 5 Pages: 476-82
  • DOI: 10.1038/gt.2011.183
  • Peer Reviewed
• [Journal Article] キメラ抗原受容体発現T細胞を用いた難治性B細胞腫瘍に対する養子免疫遺伝子療法 (2011)
  • Author(s): 塚原智典
  • Journal Title: 医学のあゆみ Volume: 237 Pages: 223-226
• [Journal Article] キメラ抗原受容体発現T細胞による癌に対する養子免疫遺伝子療法 (2010)
  • Author(s): 塚原智典
  • Journal Title: 最新医学 Volume: 65 Pages: 1813-1818
• [Journal Article] キメラ抗原受容体発現T細胞によるがんに対する養子免疫遺伝子療法 (2010)
  • Author(s): 塚原智典
  • Journal Title: 最新医学 Volume: 65(8) Pages: 1813-1818
  • NAID: 40017239752
• [Presentation] Engineered T lymphocytes expressing an anti-CD19 CAR specifically eradicate B-lymphoma cells (2011)
  • Author(s): Tomonori Tsukahara, Ken Ohmine, Ryosuke Uchibori, Masashi Urabe, Hiroaki Mizukami, Akihiro Kume, Isabelle Riviere, Michel Sadelain, Renier J.Brentjens, Keiya Ozawa
  • Organizer: 日本遺伝子治療学会
  • Place of Presentation: 九州大学百年講堂(福岡)
  • Year and Date: 2011-07-17
• [Presentation] Engineered T lymphocytes expressing an anti-CD19 CAR specifically eradicate B-lymphoma cells (2011)
  • Author(s): Tsukahara, T., Ohmine, K., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Riviere, I., Sadelain, M., Brentjens, R. J., Ozawa K.
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Fukuoka
  • Year and Date: 2011-07-07
• [Presentation] Validation of anti-tumor effects mediated by anti-CD19CAR T-cells for B cell lymphoma (2010)
  • Author(s): Tsukahara, T., Ohmine, K., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Ozawa, K.
  • Organizer: XXIII Annual Congress of the European Society of Gene and Cell Therapy
  • Place of Presentation: Milano, Italy
  • Year and Date: 2010-10-23
• [Presentation] Validation of anti-tumor effects mediated by anti-CD19CAR T-cells for B cell lymphoma (2010)
  • Author(s): T Tsukahara, K Ohmine, R Uchibori, M Urabe, H Mizukami, A Kume, I Riviere, M Sadelain, R Brentjens, K Ozawa
  • Organizer: XXIII Annual Congress of the European Society of Gene and Cell Therapy
  • Place of Presentation: Stella Polare convention center (Milano), Italia
  • Year and Date: 2010-10-23
• [Presentation] Cytotoxicity of primary T-lymphocytes expressing a chimeric antigen receptor targeting CD19 against B-cell lymphoma cells (2010)
  • Author(s): Tsukahara, T., Ohmine, K., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Ozawa, K.
  • Organizer: Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka
  • Year and Date: 2010-09-22
• [Presentation] Cytotoxicity of primary T-lymphocytes expressing a chimeric antigen receptor targeting CD19 against B-cell lymphoma cells (2010)
  • Author(s): T Tsukahara, K Ohmine, R Uchibori, M Urabe, H Mizukami, A Kume, K Ozawa
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-22
• [Presentation] Bリンパ腫細胞に対する抗CD19キメラ抗原受容体発現T細胞の細胞障害活性 (2010)
  • Author(s): 塚原智典, 大嶺謙, 内堀亮介, 卜部匡司, 水上浩明, 久米晃啓, 小澤敬也
  • Organizer: 造血器腫瘍免疫療法研究会
  • Place of Presentation: 松山
  • Year and Date: 2010-08-29
• [Presentation] Bリンパ腫細胞に対する抗CD19キメラ抗原受容体発現T細胞の細胞障害活性 (2010)
  • Author(s): 塚原智典, 大嶺謙, 内堀亮介, 卜部匡司, 水上浩明, 久米晃啓, 小澤敬也
  • Organizer: 第2回造血器腫瘍免疫療法研究会
  • Place of Presentation: 大和屋本店(松山)
  • Year and Date: 2010-08-29
• [Presentation] Ex vivo expansion of primary T-lymphocytes expressing a chimeric antigen receptor targeting CD19 with antigen stimulation (2010)
  • Author(s): Tsukahara, T., Sakurai, C., Ohmine, K., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Riviere, I., Sadelain, M., Brentjens, R. J., Ozawa K.
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Utsunomiya
  • Year and Date: 2010-07-01
• [Presentation] Ex vivo expansion of primary T-lymphocytes expressing a chimeric antigen receptor targeting CD19 with antigen stimulation (2010)
  • Author(s): Tsukahara T., Sakurai C., Ohmine K., Uchibori R., Urabe M., Mizukami H., Kume A., Riviere I., Sadelain M., Brentjens R.J., Ozawa K
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 栃木県総合文化センター(宇都宮)
  • Year and Date: 2010-07-01