Single-cell analysis of T-cell receptor repertoire of HTLV-1 Tax-specific cytotoxic T cells in patients with adult T-cell leukemia/lymphoma.

• Project/Area Number: 23501286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Jichi Medical University
• Principal Investigator: KANDA Yoshinobu 自治医科大学, 医学部, 教授 (30334379)
• Co-Investigator(Kenkyū-buntansha): YAMAZAKI Rie 自治医科大学, 医学部, 助教 (80365262)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 細胞傷害性T細胞 / レパトア / 成人T細胞性白血病 / HTLV-I / 造血幹細胞移植 / 免疫細胞療法

Research Abstract

We analyzed the T-cell receptor repertoire of HTLV-1 Tax-specific cytotoxic T cells in patients with adult T-cell leukemia/lymphoma. We found that the Tax-CTLs share P-D/P-R motif, persist as effector memory CTLs for long term after transplantation, and show universal killing activity against third-party HTLV-I infected cells. We are planning a redirected T-cell immunotherapy using T-cell receptor alpha/beta genes from these clones.

Research Products

• [Journal Article] Universal cytotoxic activity of a HTLV-1 Tax-specific T cell clone from an HLA-A*24 : 02+ patient with adult T-cell leukemia against a variety of HTLV-I-infected T-cells (2014)
  • Author(s): Yukie Tanaka, Rie Yamazaki, Kiriko Terasako-Saito, Hideki Nakasone, Yu Akahoshi, Hiroshi Nakano, Tomotaka Ugai, Hidenori Wada, Ryoko Yamasaki, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Masahiro Ashizawa, Miki Sato, Shun-ichi Kimura, Misato Kikuchi, Shinichi Kako, Junya Kanda, Aki Tanihara, Junji Nishida, Yoshinobu Kanda
  • Journal Title: Immunology Letters Volume: 158 Issue: 1-2 Pages: 120-125
  • DOI: 10.1016/j.imlet.2013.12.016
  • Peer Reviewed
• [Journal Article] Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT. (2014)
  • Author(s): Nakasone H, Tanaka Y, Yamazaki R, Terasako K, Sato M, Sakamoto K, Yamasaki R, Wada H, Ishihara Y, Kawamura K, Machishima T, Ashizawa M, Kimura SI, Kikuchi M, Tanihara A, Kanda J, Kako S, Nishida J, Kanda Y.
  • Journal Title: Bone Marrow Transplant Volume: 49 Issue: 1 Pages: 87-94
  • DOI: 10.1038/bmt.2013.122
  • Peer Reviewed
• [Journal Article] Impact of high-/middle-molecular-weight adiponectin on the synthesis and regulation of extracellular matrix in dermal fibroblasts (2014)
  • Author(s): Hideki Nakasone, Kiriko Terasako-Saito, Rie Yamazaki, Miki Sato, Yukie Tanaka, Kana Sakamoto, Masakazu Kurita,, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Tomohito Machishima, Masahiro Ashizawa, Shun-ichi Kimura, Misato Kikuchi, Aki Tanihara, Junya Kanda, Shinichi Kako, Junji Nishida, Shigeki Yamada and Yoshinobu Kanda
  • Journal Title: Experimental Hematology Volume: (in press) Issue: 4 Pages: 261-273
  • DOI: 10.1016/j.exphem.2013.12.009
• [Journal Article] Allotype Analysis to Distinguish the Origin of Varicella-Zoster Virus Immunoglobulin G After Allogeneic Stem Cell Transplantation. (2013)
  • Author(s): Yamazaki R, Nakasone H, Kanda Y, et al.
  • Journal Title: Biol Blood Marrow Transplant Volume: in press Issue: 7 Pages: 1013-1020
  • DOI: 10.1016/j.bbmt.2013.04.007
  • Peer Reviewed
• [Journal Article] Long-term persistence of limited HTLV-I Tax-specific cytotoxic T cell clones in a patient with adult T cell leukemia/lymphoma after allogeneic stem cell transplantation. (2012)
  • Author(s): Tanaka Y, Nakasone H, Yamazaki R, Kanda Y, et al.
  • Journal Title: J Clin Immunol Volume: 32 Issue: 6 Pages: 1340-1352
  • DOI: 10.1007/s10875-012-9729-5
  • Peer Reviewed
• [Journal Article] Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation : a nationwide retrospective study (2012)
  • Author(s): Junya Kanda
  • Journal Title: Blood Volume: 119 Issue: 10 Pages: 2409-2416
  • DOI: 10.1182/blood-2011-08-372573
  • Peer Reviewed
• [Journal Article] Recurrence of monoclonal gammopathy associated with donor-derived myelodysplastic syndrome after cord blood stem cell transplantation. (2011)
  • Author(s): Rie Yamazaki, Yoshinobu Kanda, et al.
  • Journal Title: Experimental Hematology Volume: 39 Issue: 12 Pages: 1119-1123
  • DOI: 10.1016/j.exphem.2011.09.002
  • Peer Reviewed
• [Journal Article] Immune recovery after autologous peripheral blood stem cell transplantation without in vitro graft manipulation for refractory systemic lupus erythematosus. (2011)
  • Author(s): Hidenori Wada, Rie Yamazaki, Yoshinobu Kanda, et al.
  • Journal Title: Bone Marrow Transplantation Volume: 46 Issue: 11 Pages: 1450-1454
  • DOI: 10.1038/bmt.2010.332
  • Peer Reviewed