Investigation of redirected Tax-specific T-cell immunotherapy against adult T-cell leukemia/lymphoma

2016 Fiscal Year Final Research Report

• Project/Area Number: 26290058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• 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): 諫田 淳也 自治医科大学, 医学部, 講師 (30636311) ; 仲宗根 秀樹 自治医科大学, 医学部, 講師 (50757903) ; 山崎 理絵 自治医科大学, 医学部, 助教 (80365262)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 遺伝子導入免疫細胞療法

Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy caused by HTLV-I infection. ATL is refractory to chemotherapy and the prognosis of patients with ATL is extremely poor. We have revealed that cytotoxic T-cells (CTLs) against Tax, a protein produced by HTLV-I, increased after allogeneic hematopoietic stem cell transplantation for ATL and found that CTLs with T-cell receptor (TCR) repertoir containing "PDR" motif exhibit strong cytotoxic activity against HTLV-I infected cells. In addition, we produced redirected Tax-specific CTL by transducing the full-length TCR alpha and beta genes of the "PDR"-containing TCR to peripheral blood mononuclear cells from healthy volunteers using retroviral vector, and showed that the redirected CTLs also had strong cytotoxic activity against HTLV-I infected cells both in vitro and in vivo (patent pending).

Free Research Field

血液内科学