Preclinical research for the clinical application of T-cell receptor gene therapy targeting tax for adult T-cell leukemia/lymphoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• 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): 仲宗根 秀樹 自治医科大学, 医学部, 講師 (50757903)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 免疫細胞療法 / 成人T細胞性白血病 / 遺伝子治療

Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma is a hematological malignancy caused by Human T-cell Leukemia Virus Type 1 (HTLV-I). We have previously transduced TCR-alpha/beta genes, cloned from a tax-specific CTL clone, into peripheral blood mononuclear cells (PBMCs) of healthy volunteers, and those cells showed strong cytotoxic activity against HTLV-I infected cells. In this study, we identified an ideal condition to transduce those genes into PBMCs from patients with ATL, because we are planning to use autologous gene-modified cells in clinical settings. In addition, we have established a blood test tool to quantitate Tax mRNA, and currently developing it as a companion diagnostic test to evaluate the sensitivity to Tax-specific immunotherapy.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

成人T 細胞白血病・リンパ腫(ATL)は極めて難治性の造血器腫瘍であり、同種造血幹細胞移植が唯一の根治的治療法であるが、その予後も決して優れたものではなく、また、同種造血幹細胞移植を受けることができる患者も限られている。そのため、新しい治療法の開発が熱望されている。本研究のTax特異的T細胞受容体遺伝子導入免疫細胞療法は、既存の治療法とは全く異なり機序で抗腫瘍効果をもたらすものであり、本研究成果によって、今後、この治療法を診療現場に届けための医師主導治験につなげることができる。