The development of iPSC-derived CTL therapy for EBV-associated lymphoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09842
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Juntendo University
• Principal Investigator: Ando Miki 順天堂大学, 医学部, 准教授 (10424251)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: CTL / iPSC由来若返りCTL / EBウイルス関連リンパ腫

Outline of Final Research Achievements

Antigen-specific T lymphocytes (CTL) generated from iPSC have higher proliferative capacity and longer telomeres than the original CTL and are functionally rejuvenated (rejT). We could generate EBV-CTL clones from donors and T-iPSCs were subsequently established from each CTL clone. All T-iPSCs derived from various EBV antigen-specific CTLs efficiently differentiated into rejT. These rejT had equally high specificity while showing stronger cytotoxicity against EBV-infected tumor cell lines when compared to the original EBV-CTL. We also demonstrated prolonged and robust eradication of EBV+ NK cell lymphoma in vivo by EBV-rejT, with rejT persisting as central memory T cells in mouse spleen for at least 6 months. We believe that rejT therapy provides a promising and safe approach to “off-the-shelf therapy” for EBV-associated lymphomas.

Free Research Field

血液学、再生医学、遺伝子免疫細胞療法

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、iPS細胞由来EBウイルス特異的CTLを用いた細胞療法が難治性のEBウイルス関連リンパ腫の強力な新規治療法となる可能性を示唆した。また、投与したiPS細胞由来EBウイルス特異的CTLが生体内で長期にわたって生存し、腫瘍を排除し続けるという結果はT細胞の若返りという意味でも非常に有望であり、我々の研究グループが計画を進めている「EBウイルス関連リンパ腫に対するiPS細胞由来若返りT細胞療法」の臨床研究実現化に向けた大きな加速が予想される。