Immunotherapy for ATL using specific chimeric antigen receptor

• Project/Area Number: 25461427
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kagoshima University
• Principal Investigator: Yoshimitsu Makoto 鹿児島大学, 医歯学域医学系, 准教授 (70404530)
• Co-Investigator(Kenkyū-buntansha): ITOH Yuji 鹿児島大学, 理工学域理学系, 教授 (60223195)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: CART療法 / T細胞受容体 / CART / TCR / NOJマウス / 成人T細胞白血病リンパ腫 / 免疫不全マウス / 異種移植

Outline of Final Research Achievements

Adult T cell lekukemia/lymphoma is a retractable hematological malignancy, which requires effective therapeutic modality. It is very important for immunotherapy using chimeric antigen receptor T cell to identify therapeutically relevant target antigen. Here we assessed T cell receptor repertoire among patients with ATL. We found that T cell receptor V beta 2 was the most prevalent TCR, more than 15% of ATL patients express TCRVb2. After cloning of TCRVb2 by RACE, we developed TCRVb2 expressing lentiviral vector and establish TCRVb2 highly expressing cell line. We tried to identify anti-TCRVb2 specific antibody by phage display library. Further optimization of this protocol need to be explored.

Research Products

• [Journal Article] A new ATL xenograft model and evaluation of pyrrolidine dithiocarbamate as a potential ATL therapeutic agent. (2015)
  • Author(s): Nakamura D, Yoshimitsu M, Kuroki A, Hachiman M, Kamada Y, Ezinne CC, Arai A, Inoue H, Hamada H, Hayashida M, Suzuki S, Fujino S, Arima N, Arima M, Tabuchi T, Okada S, Arima N.
  • Journal Title: Experimental Hematology Volume: 43 Issue: 11 Pages: 944-950
  • DOI: 10.1016/j.exphem.2015.06.303
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] HTLV-1 specific CD8 + T Cell Function Augmented by blockade of 2B4/CD48 Interaction in HTLV-1 Infection. (2014)
  • Author(s): Chibueze C.E, Yoshimitsu M, White Y, Arima N.
  • Journal Title: Plos One Volume: 9 Issue: 2 Pages: 87631-87631
  • DOI: 10.1371/journal.pone.0087631
  • Peer Reviewed